Drug delivery using monoacylglycerol and free fatty acid based compositions

Abstract

Compositions and methods are disclosed for preparing nanoemulsions from oils. These nanoemulsions can be produced without the addition of exogenous surfactants or emulsifiers and can be useful as carriers for active ingredients.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 174,487, filed April 13, 2021, U.S. Provisional Patent Application No. 63 / 174,489, filed April 13, 2021, U.S. Provisional Patent Application No. 63 / 197,896, filed June 7, 2021, U.S. Provisional Patent Application No. 63 / 197,905, filed June 7, 2021, and U.S. Provisional Patent Application No. 63 / 292,862, filed December 22, 2021, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] There are several methods by which emulsions can be generated outside the body. However, these nanoemulsion formulations generally require the addition of other agents (e.g., surfactants such as Tween-80 (polysorbate 80)) to stabilize the nanoemulsion. There is an unmet need for nanoemulsion formulations that do not require additional stabilizers, emulsifiers, or surfactants and are stable.

[0003] Emulsions, including nanoemulsions and microemulsions, can be useful as carriers for active ingredients, such as pharma- ceutical active substances.

[0004] Enzymatic hydrolysis of commercial crude oils, primarily composed of triglycerides, can be achieved by selective use of lipases to provide access to MAGs and FFAs and yield the desired overall ratio of material, while molecular distillation can be used to purify the individual components. Major components present in crude oils, such as terpenes, terpenoids, sterols, polyphenols, phytosterols, etc., can contribute properties to the hydrolyzed triglycerides that can enhance biological activity compared to the individual MAG and FFA components typically studied, such as those from distillation.

[0005] There is a need for oil formulations containing specific oil combinations that can provide a drug delivery system by carrying active ingredients, such as pharma- ceutical active substances. Summary of the Invention

[0006] The present disclosure is directed to an oil composition that can include enzyme modified oil (EMO) and / or free fatty acid (FFA) oil and can be used in combination with an active ingredient. The oil composition of the present disclosure can be used in any formulation, but can also be used to formulate nanoemulsions and microemulsions containing free fatty acid and, optionally, monoacylglycerol (MAG) and / or diacylglycerol (DAG), which do not require additional agents to stabilize the nanoemulsion. Methods for making the same are provided in addition to methods of use, which include administering to a subject a formulation containing the active ingredient and / or the oil composition. In certain embodiments, the composition of the present disclosure can provide enhanced permeability to the active ingredient.

[0007] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight free fatty acids (FFAs), the FFAs comprising two or more different fatty acids, the oil comprising 80% or less by weight triacylglycerols (TAGs) of the total weight of the oil, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0008] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight of FFA and no more than 80% by weight of TAG, the oil comprising non-oil components naturally present in the oil, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0009] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) in an amount of at least 5 wt. % of the total weight of the oil, the MAG and the FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0010] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAG in an amount of at least 5 wt. % of the total weight of the oil, the MAG and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0011] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) and diacylglycerol (DAG) in an amount of at least 5 wt. % of the total weight of the oil, the MAG and FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0012] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAGs and DAGs in an amount of at least 5 wt. % of the total weight of the oil, the MAGs and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0013] In some embodiments, a method is provided for preparing a nanoemulsion comprising providing an oil of the present disclosure, providing a polar liquid component, combining the oil and the polar liquid component to form a nanoemulsion premix, and forming a nanoemulsion from the nanoemulsion premix, wherein the nanoemulsion comprises an oil phase and a polar liquid phase, wherein the oil phase is dispersed as droplets or particles within the polar liquid phase, and the droplets or particles have a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0014] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight free fatty acids (FFAs), the FFAs comprising two or more different fatty acids, the oil comprising 80% or less by weight triacylglycerols (TAGs) of the total weight of the oil, and the droplets or particles having a Z-average size of greater than about 300 nm as measured by dynamic light scattering.

[0015] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight of FFA and no more than 80% by weight of TAG, the oil comprising non-oil components naturally occurring in the oil, and the droplets or particles having a Z-average particle size of greater than about 300 nm as measured by dynamic light scattering.

[0016] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) in an amount of at least 5 wt. % of the total weight of the oil, the MAG and the FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of greater than about 300 nm as measured by dynamic light scattering.

[0017] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAG in an amount of at least 5 wt. % of the total weight of the oil, the MAG and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of greater than about 300 nm as measured by dynamic light scattering.

[0018] In some embodiments, a composition is provided comprising an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight of FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) and diacylglycerol (DAG) in an amount of at least 5% by weight of the total weight of the oil, the MAG and FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of greater than about 300 nm as measured by dynamic light scattering.

[0019] In some embodiments, a composition is provided comprising an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAGs and DAGs in an amount of at least 5 wt. % of the total weight of the oil, the MAGs and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of greater than about 300 nm as measured by dynamic light scattering.

[0020] In some embodiments, a method is provided for preparing a nanoemulsion or microemulsion comprising providing an oil of the present disclosure, providing a polar liquid component, combining the oil and the polar liquid component to form a nanoemulsion premix, and forming a nanoemulsion from the nanoemulsion premix, wherein the nanoemulsion comprises an oil phase and a polar liquid phase, the oil phase is dispersed as droplets or particles within the polar liquid phase, and the droplets or particles have a Z-average size of greater than about 300 nm as measured by dynamic light scattering.

[0021] In some embodiments, an oil composition is provided that may comprise monoacylglycerols (MAGs) in an amount of about 10% to about 80% by weight of the total weight of the oil, free fatty acids (FFAs) in an amount of about 5% to about 75% by weight of the total weight of the oil, applicable based on weight percentage of MAGs, a combination of MAGs and FFAs being about 60% to about 95% by weight of the total weight of the oil, the FFAs comprising two or more different fatty acids, and the oil being substantially free of triacylglycerols (TAGs).

[0022] In some embodiments, a pharmaceutical composition is provided comprising a composition of the present disclosure and an active ingredient.

[0023] In some embodiments, a method of delivering an active ingredient to a subject can include administering to a subject a pharmaceutical composition of the present disclosure. [Brief description of the drawings]

[0024] [Figure 1] 1 shows the size distribution as measured by dynamic light scattering for Example 2. [Figure 2A] 1 shows the Z-average particle size as measured by dynamic light scattering over time for flaxseed EMO nanoemulsion samples stored at room temperature (data are expressed as the mean ± SD from at least three measurements). [Figure 2B] Z-average particle size as measured by dynamic light scattering over time for sesame EMO nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2C] Z-average particle size as measured by dynamic light scattering over time for coconut EMO / medium chain fatty acid (MCT) FFA oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2D]Figure 1 shows the Z-average particle size as measured by dynamic light scattering over time for MCT EMO / coconut FFA oil nanoemulsion samples stored at room temperature (data are presented as the mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2E] Z-average particle size as measured by dynamic light scattering over time for fish EMO / linseed FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2F] Z-average particle size as measured by dynamic light scattering over time for flaxseed EMO / fish FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2G] Z-average particle size as measured by dynamic light scattering over time for fish EMO / coconut FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2H] Z-average particle size as measured by dynamic light scattering over time for flaxseed EMO / coconut FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2I] Z-average particle size as measured by dynamic light scattering over time for coconut EMO / linseed FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2J]Z-average particle size as measured by dynamic light scattering over time for MCT EMO oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2K] Z-average particle size as measured by dynamic light scattering over time for olive oil EMO nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2L] Z-average particle size as measured by dynamic light scattering over time for rosehip EMO / coconut FFA oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2M] Z-average particle size as measured by dynamic light scattering over time for coconut EMO / rosehip FFA oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2N] Z-average particle size as measured by dynamic light scattering over time for rosehip EMO / linseed FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2O] Z-average particle size as measured by dynamic light scattering over time for flaxseed EMO / rosehip FFA oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2P]Z-average particle size as measured by dynamic light scattering over time for rosehip EMO nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2Q] Figure 1 shows the Z-average particle size as measured by dynamic light scattering over time for hemp seed EMO nanoemulsion samples stored at room temperature (data are presented as the mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2R] Z-average particle size as measured by dynamic light scattering over time for algal EMO / linseed FFA oil nanoemulsion samples stored at room temperature (data are expressed as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Figure 2S] Z-average particle size as measured by dynamic light scattering over time for algal EMO / MCT FFA oil nanoemulsion samples stored at room temperature (data are presented as mean ± SD from at least three measurements, precipitated formulations were assigned a Z-average size of 1000 nm). [Diagram 3] Shown is the size distribution for almond oil mixed micellar nanoemulsion (MMN) 102919.1 3X. [Figure 4] Zeta potential for almond oil MMN102919.1 3X is shown. [Diagram 5] 4 shows the size distribution for almond oil MMN111819.1. [Figure 6] The cumulative amount of hydrocortisone permeated through the Strat-M® membranes over 7 hours from nS50, micro-S50, nano-TAG, and free drug control is shown (data presented as mean ± SD, n=2). [Figure 7]The cumulative amount of hydrocortisone permeated through the Strat-M® membrane from drug-loaded (nS50-loaded HCT and micro-S50-loaded HCT) and unloaded (nS50+HCT DMSO and micro-S50+HCT DMSO) formulations over 7 hours is shown (data presented as mean ± SD, n=2). [Figure 8] 1 shows the cumulative amount of hydrocortisone permeated through the Strat-M® membrane over 7 hours from nFx0, nOa / Fx25, nOA / Fx50 and nOa / Fx75 formulations (data presented as mean ± SD, n=2). [Figure 9] The cumulative amount of hydrocortisone permeated through the Strat-M® membrane over 7 hours from nS25, nS50, and nS75 formulations is shown (data presented as mean ± SD, n=2). [Figure 10] 1 shows the cumulative amount of hydrocortisone permeated through the Strat-M® membrane after 7 hours from flaxseed, oat, sesame, rosehip, almond, hemp, and MCT EMO nanoemulsions and HCT control (10% DMSO) (data presented as mean ± SD, n=2). [Figure 11] 1 shows the cumulative amount of hydrocortisone permeated through a Strat-M® membrane from Cerave cream with or without 10% oat EMO over a 7-hour period (data presented as mean ± SD, n=2). [Figure 12] Figure 1 shows cumulative salicylic acid permeated through the Strat-M® membrane over time. Data presented as mean + / - standard deviation (n=2). [Figure 13A] 1 shows the cumulative salicylic acid permeated over time for CHARLOTTE'S WEB CBDMEDIC Acne Treatment Cream with and without 10% Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13B] 1 shows cumulative salicylic acid permeated over time for CERAVE Acne Control Gel with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13C] 1 shows cumulative salicylic acid permeated over time for CERAVE Body Wash for Rough and Bumpy Skin with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13D] 1 shows cumulative salicylic acid transmitted over time for CLEARASIL Stubborn Acne Control + Marks 1 Minute Mask with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13E] 1 shows cumulative salicylic acid permeated over time for NEUTROGENA Rapid Clear Acne Clearing Spot Gel with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13F] 1 shows cumulative salicylic acid permeated over time for CLEARASIL Rapid Rescue Spot Treatment Gel with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 13G] 1 shows cumulative salicylic acid permeated over time for CERAVE Psoriasis Moisturizing Cream with and without 10% Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 14] Figure 1 shows cumulative salicylic acid permeated over time for CERAVE Psoriasis Moisturizing Cream with or without EMO / FFA oil in nanoemulsion or non-nanoemulsion form. Data presented as mean + / - standard deviation (n=2). [Figure 15] Figure 2 shows cumulative bupivacaine HCl permeated over time with and without sesame EMO nanoemulsion in Example 20. Data presented as mean + / - standard deviation (n=2). [Figure 16A] Cumulative lidocaine permeated over time in ASPERCREME with and without EMO. Data presented as mean + / - standard deviation (n=2). [Figure 16B]Cumulative lidocaine permeated over time in ASPERCREME with and without EMO. Data presented as mean + / - standard deviation (n=2). [Figure 16C] Figure 1 shows cumulative lidocaine permeated over time from ASPERCREME and lidocaine carbomer formulations with and without Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 16D] 1 shows cumulative lidocaine permeated over time from ASPERCREME and lidocaine carbomer formulations with Sesame EMO at various lidocaine levels. Data presented as mean + / - standard deviation (n=2). [Figure 17A] Cumulative prilocaine permeated over time from EMLA with and without Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 17B] Cumulative lidocaine permeated over time from EMLA with and without Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 18] 1 shows cumulative diclofenac permeated over time from VOLTAREN cream with and without sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 19] Figure 1 shows cumulative CBD permeated over time from GARDEN OF LIFE Intensive Recovery Cream with and without EMO. Data presented as mean + / - standard deviation (n=2). [Figure 20] 1 shows cumulative resveratrol permeated over time from SkinCeuticals Resveratrol BE Cream with and without EMO. Data presented as mean + / - standard deviation (n=2). [Figure 21A] 1 shows cumulative retinyl palmitate transmitted over time from REVITALIFT Anti-Wrinkle Eye Cream with and without Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 21B]Figure 1 shows cumulative retinyl palmitate permeated over time from REVITALIFT Anti-Wrinkle Moisture Cream with and without Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 21C] 1 shows cumulative retinyl palmitate permeated over time from REVITALIFT Cica Cream with and without Oat EMO. Data presented as mean + / - standard deviation (n=2). [Figure 22A] 1 shows cumulative retinol transmitted over time for NEUTROGENA Ageless Intensive Anti-Wrinkle Cream with and without 10% Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 22B] Figure 1 shows cumulative retinol transmitted over time for NEUTROGENA Healthy Skin Anti-Wrinkle Night Cream with and without 10% Sesame EMO. Data presented as mean + / - standard deviation (n=2). [Figure 23] Figure 1 shows cumulative trifluoroacetyl tripeptide-2 over time from sesame EMO nanoemulsion and free peptide control. Data presented as mean + / - standard deviation (n=2). [Figure 24] Cumulative hexapeptide-11 permeated over time from sesame EMO nanoemulsion and free peptide control. Data presented as mean + / - standard deviation (n=2). [Diagram 25] Cumulative 5-fluorouracil (5-FU) permeated over time from a prescribed cream with or without 10% EMO. Data presented as mean + / - standard deviation (n=2). [Figure 26] 1 shows the measurement of non-oil components in unmodified canola oil and canola EMO. [Figure 27] Figure 1 shows cumulative lidocaine permeated over time from ASPERCREME with or without sesame EMO, EMO / FFA oil, FFA oil, or TAG oil. Data presented as mean + / - standard deviation (n=2). [Figure 28]Figure 1 shows cumulative hydrocortisone permeated over time from ASPERCREME with or without sesame EMO, EMO / FFA oil, FFA oil, or TAG oil. Data presented as mean + / - standard deviation (n=2). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] The present disclosure is directed to an oil composition that can include enzyme modified oil (EMO) and / or free fatty acid (FFA) oil and can be used in combination with an active ingredient or to create nano- and micro-emulsions. The oil composition of the present disclosure can be used in any formulation, but can also be used to formulate nano- and micro-emulsions containing free fatty acid and, optionally, monoacylglycerol (MAG) and / or diacylglycerol (DAG), which do not require additional agents to stabilize the nano-emulsion. Methods for making the same are provided in addition to methods of use, which include administering to a subject a formulation containing the active ingredient and / or the oil composition. In certain embodiments, the composition of the present disclosure can provide enhanced permeability to the active ingredient.

[0026] It is to be understood that both the foregoing summary and the following detailed description are exemplary and explanatory only and are not restrictive of the claimed invention. In this application, the use of the singular includes the plural unless otherwise stated, the word "a" or "an" means "at least one," and the use of "or" means "and / or." Furthermore, the terms "including," as well as other forms of "includes" and "included," are not limiting.

[0027] The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including but not limited to patents, patent applications, articles, books, and papers, are expressly incorporated herein by reference in their entirety for any purpose. In the event that one or more of the incorporated literature and similar materials defines a term in a manner that contradicts the definition of that term in this application, this application shall control.

[0028] definition As used herein, "nanoemulsion" refers to a colloidal particle system consisting of two immiscible liquids, or a liquid and a solid, where one liquid or solid (the dispersed phase) is dispersed as droplets or particles, respectively, in the other liquid (the continuous phase). A "nanoemulsion" can contain droplets or particles with sizes between 10 and 1000 nm, but generally, to be kinetically stable, a nanoemulsion must have a small droplet size (<300 nm). The dispersed phase is also known as the discontinuous phase, while the outer phase can be referred to as the continuous phase.

[0029] As used herein, "microemulsion" refers to a colloidal particle system consisting of two immiscible liquids, or a liquid and a solid, where one liquid or solid (the dispersed phase) is dispersed as droplets or particles, respectively, in the other liquid (the continuous phase). "Microemulsions" can include droplets or particles having sizes from 1000 nm to greater than 1,000,000 nm.

[0030] As used herein, "free fatty acids (FFA)" refers to non-esterified fatty acids in their carboxylic acid or carboxylate form.

[0031] As used herein, "monoacylglycerol (MAG)," also known as a monoglyceride, is a glyceride consisting of one fatty acid chain covalently attached to a glycerol molecule via an ester bond.

[0032] As used herein, "diacylglycerol (DAG)," also known as a diglyceride, is a glyceride consisting of two fatty acid chains covalently attached to a glycerol molecule via an ester bond.

[0033] As used herein, "triacylglycerol (TAG)", also known as triglyceride, is a glyceride consisting of three fatty acid chains covalently attached to a glycerol molecule via ester bonds. TAGs may also be classified as having long or medium chain lengths. Long chain TAGs contain fatty acids with 14 or more carbons, and medium chain TAGs contain fatty acids with 6-12 carbons. Long chain TAGs can contain omega-3 and omega-6 fatty acids. Medium chain TAGs have saturated fatty acids and therefore do not contain omega-3 or omega-6 fatty acids. Long chain TAGs (LCTs) and medium chain fatty acids (MCTs) can function as energy sources.

[0034] As used herein, "exogenous additives having surfactant and / or emulsifier properties" refers to compounds that function as surfactants or emulsifiers, which are added to the oil but do not naturally occur in the oil in sufficient amounts to enhance the formation and stability of droplets or particles in the nanoemulsion. Non-limiting examples of surfactants are 4-(5-dodecyl)benzenesulfonate, docusate (dioctyl sodium sulfosuccinate), alkyl ether phosphates, benzalkonium chloride (BAC), and perfluorooctane sulfonate (PFOS). Non-limiting examples of emulsifiers include ethoxylated alcohols, carboxylates, sodium isothionate, cetyl alcohol, stearyl alcohol, and silicone emulsifiers such as dimethicone.

[0035] As used herein, "exogenous additives with thickening or crystallization-inhibiting properties" refer to thickeners or crystallization inhibitors that are added to oils in sufficient amounts to thicken or inhibit crystallization of the nanoemulsion, respectively, but that are not naturally present in the oil. By way of example and without limitation, such exogenous additives with thickening properties can include methylcellulose, corn starch, sodium alginate, and gelatin. By way of example and without limitation, such exogenous additives with crystallization-inhibiting properties can include polyglycerol fatty acid esters, sucrose fatty acid esters, and sorbitan fatty acid esters.

[0036] As used herein, "surfactant" or "emulsifier" refers to a substance that reduces the surface tension between two liquids, or in the case of solid lipid nanoemulsions, between the liquid phase and the solid lipid phase. Surfactants, or surface active agents, are compounds that reduce the surface tension between two liquids, or between a liquid and a solid. Emulsifiers are surfactants that stabilize emulsions. Emulsifiers coat the droplets in an emulsion and prevent them from joining together or flocculating.

[0037] Surfactants are generally used as emulsifiers because they are known to stabilize emulsifiers.By way of example and without limitation, surfactants (and emulsifiers) can include polysorbates, phospholipids, sterols, cationic lipids, poloxamers, sorbitan esters, sugar esters, polyoxyethylene conjugates, phosphatidyl lapsidate ammonium, polyphenols, polyvinyl alcohol, lecithin, ethanol, lysophospholipids, ceramides, tween, span, corifol, propylene glycol, vitamin D, polyethylene glycol, polyethylene glycol derivatives, pectin, gum acacia, modified gum acacia, agar, ghatti gum, modified ghatti gum, pectin, carrageenan, xanthan gum, modified starch, modified alginate, fatty alcohol, and ethoxylated polyol.

[0038] As used herein, "enzymatically modified oil (EMO)" refers to an oil comprising MAGs, and optionally some DAGs, and / or FFAs, which is obtained by enzymatic hydrolysis of a starting oil source to obtain FFAs and glycerol, followed by separation of the glycerol and at least partial enzymatic re-esterification of the glycerol with FFAs to obtain MAGs, and optionally some DAGs, and / or in some instances, residual FFAs. Unless otherwise specified herein, EMO should be understood to be substantially free (below detectable levels) of TAGs. In some embodiments, EMO can have less than 5% TAGs.

[0039] As used herein, "free fatty acid oil (FFA oil)" refers to an oil that contains free fatty acids resulting from enzymatic hydrolysis of TAG in a starting oil source into FFAs and glycerol, followed by removal of the glycerol. It is understood that the FFA oil can contain some glycerol that can be dissolved in the FFA oil.

[0040] Methods for producing EMO and FFA oils, and properties thereof, are disclosed in International Patent Application No. PCT / US2018 / 055583, filed October 12, 2018, published as WO2019 / 075307 and PCT / US2020 / 014182, filed January 17, 2020, and published as WO2020 / 150661, and U.S. Patent Application Publication No. 2020 / 0146307 (U.S. Ser. No. 16 / 746,700), each of which is incorporated herein by reference in its entirety.

[0041] As used herein, "non-oil components" are components naturally occurring in the oil source that are not MAGs, DAGs, TAGs, or FFAs.

[0042] As used herein, "therapeutically effective amount" refers to the amount of the composition of the present disclosure that effectively produces the desired therapeutic response. By way of example, and not by way of limitation, an amount that is effective for slowing the growth of cancer or shrinking cancer, or for reducing pain or inflammation, may be a "therapeutically effective amount". The specific therapeutically effective amount will vary depending on factors such as the specific condition being treated, the physical condition of the subject, the type of subject being treated, the duration of treatment, the nature of the combination therapy (if any), and the specific formulation being used, as well as the structure of the composition.

[0043] As used herein, an "active ingredient" is a substance intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure or function of the body of a subject, such as a mammal, preferably a human. By way of example and without limitation, an active ingredient can be a pharma- ceutically active substance, including, but not limited to, steroids, peptides, proteins, synthetic chemical molecules, plant extracts, vitamins, nucleic acids, and antioxidants.

[0044] As used herein, a "subject" refers to any living organism, such as a human or an animal.

[0045] Two important factors can determine the potential success of emulsion formation and stability-interfacial tension and repulsion by charge.

[0046] The surface tension of a fluid determines its tendency to form an emulsion. Surface tension can be reduced by adding a surfactant. Most surfactants are amphiphilic compounds. Emulsifiers can be concentrated at the oil-water interface, resulting in a significant reduction in the interfacial tension and, as a consequence, in the energy to form an emulsion. Despite the reduction in interfacial tension upon addition of a surfactant, the free energy of the interface remains positive, leaving a persistent state of thermodynamic instability.

[0047] The stability of emulsions can be improved by adding emulsifiers. Emulsifiers often have a hydrophobic end (e.g., long-chain hydrocarbons) and a charged end (e.g., carboxylic acids). The emulsifier coats the surface of the droplets or particles. Emulsion stability is often explained by the presence of repulsive charges on the surface of the emulsion droplets. If the magnitude of this energy barrier exceeds the kinetic energy of the particles, the suspension is stable. The zeta potential ("zeta potential") is a typical measure of repulsion. In general, a zeta potential of + / - 30 mV or more ensures good stability.

[0048] The size of nanoemulsion discontinuous phase particles / droplets can typically be measured using dynamic light scattering (DLS). DLS is a non-invasive and well-established technique for measuring the size and size distribution of molecules and particles, typically in the submicron region. Brownian motion of particles or molecules in suspension causes laser light to scatter at different intensities, varying over time due to constructive and destructive interference. Analysis of these intensity fluctuations yields the underlying diffusion coefficient, and therefore the particle size, using the Stokes-Einstein relationship. Typical results can include: (1) the mean or "Z-average size", i.e., the overall average size defined via a simple cumulative fit; (2) the polydispersity index (PDI), i.e., a measure of how broadly a (forced) single Gaussian peak must fit the results (0.0 being perfectly monodisperse and 1.0 being extremely polydisperse); or (3) a size distribution obtained from a multi-peak analysis with the mean peak size and standard deviation of each peak indicated, as well as the relative signal intensities (% intensity) derived from the species. The size can generally be expressed as "diameter in nanometers" (d, nm).

[0049] Zeta potential can be defined as the potential difference between the dispersion medium and a stationary layer of fluid attached to the particles, and can be measured by electrophoretic light scattering (ELS). ELS is a technique that can be used to measure the electrophoretic mobility of particles in a dispersion, or molecules in a solution. This mobility is often converted to a zeta potential to allow comparison of materials under different experimental conditions. The concept is similar to DLS, but the mobility and intensity variations are studied under the influence of an applied electric field. The basic physical principle is that of electrophoresis. The dispersion is introduced into a cell containing two electrodes. An electric field is then applied to the electrodes, and particles or molecules with a net charge move towards the electrode with the opposite charge at a speed known as mobility, which is related to their zeta potential. Typical results can include: (1) zeta potential, i.e., the overall average zeta potential of the dispersed, e.g., oil particles, in the sample, or (2) electrical conductivity, electrophoretic mobility is often also reported in mS / cm.

[0050] Nanoemulsion Composition In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight free fatty acids (FFAs), the FFAs comprising two or more different fatty acids, the oil comprising 80% or less by weight triacylglycerols (TAGs) of the total weight of the oil, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0051] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2% by weight of FFA and no more than 80% by weight of TAG, the oil comprising non-oil components naturally present in the oil, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0052] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) in an amount of at least 5 wt. % of the total weight of the oil, the MAG and the FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0053] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAG in an amount of at least 5 wt. % of the total weight of the oil, the MAG and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0054] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil comprising monoacylglycerol (MAG) and diacylglycerol (DAG) in an amount of at least 5 wt. % of the total weight of the oil, the MAG and FFAs being derived from a common first oil source, and the droplets or particles having a Z-average particle size of about 300 nm or less as measured by dynamic light scattering.

[0055] In some embodiments, a composition is provided that comprises an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising at least 2 wt. % FFAs, the FFAs comprising two or more different fatty acids, the oil also comprising MAGs and DAGs in an amount of at least 5 wt. % of the total weight of the oil, the MAGs and FFAs being derived from a first oil source and a second oil source, respectively, and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering.

[0056] In any of the foregoing embodiments, the oil can comprise at least 2% by weight of FFA oil. By way of example and not limitation, the oil can comprise at least 2% by weight, at least 3% by weight, at least 4% by weight, at least 5% by weight, at least 6% by weight, at least 7% by weight, at least 8% by weight, at least 9% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, at least 75% by weight, at least 80% by weight, at least 85% by weight, at least 90% by weight, at least 95% by weight of FFA oil. By way of further example, and without limitation, the oil may be present in an amount of about 2% to about 99% by weight, about 5% to about 99% by weight, about 10% to about 99% by weight, about 15% to about 99% by weight, about 20% to about 99% by weight, about 25% to about 99% by weight, about 30% to about 99% by weight, about 35% to about 99% by weight, about 40% to about 99% by weight, about 50% to about 99% by weight, about 60% to about 99% by weight, about 70% to about 99% by weight, about 80% to about 99% by weight, about 85% to about 99% by weight, about 90 ... 0% to approximately 99% by weight, approximately 70% to approximately 99% by weight, approximately 80% to approximately 99% by weight, approximately 90% to approximately 99% by weight, approximately 5% to approximately 90% by weight, approximately 5% to approximately 80% by weight , about 5% to about 75% by weight, about 5% to about 70% by weight, about 5% to about 60% by weight, about 5% to about 50% by weight, about 5% to about 40% by weight, about 5% to about 30% by weight, about 5% to about 25% by weight, about 5% to about 20% by weight, about 5% to about 10% by weight, about 10% to about 90% by weight, about 10% to about 80% by weight, about 10% to about 75% by weight , about 10% to about 70% by weight, about 10% to about 60% by weight, about 10% to about 50% by weight, about 10% to about 40% by weight, about 10% to about 30% by weight, about 10% to about 2 5% by weight, about 10% to about 20% by weight, about 20% to about 90% by weight, about 20% to about 80% by weight, about 20% to about 75% by weight, about 20% to about 70% by weight, about 20% by weight Amount% to about 60% by weight, about 20% to about 50% by weight, about 20% to about 40% by weight, about 20% to about 30% by weight, about 20% to about 25% by weight, about 25% to about 90% by weight,Approximately 25% to approximately 80% by weight, approximately 25% to approximately 75% by weight, approximately 25% to approximately 70% by weight, approximately 25% to approximately 60% by weight, approximately 25% to approximately 50% by weight, approximately 25% by weight %~about 40 weight%, about 25 weight%~about 30 weight%, about 30 weight%~about 90 weight%, about 30 weight%~about 80 weight%, about 30 weight%~about 75 weight%, about 30 weight%~about 70 Weight%, approximately 30% to approximately 60% by weight, approximately 30% to approximately 50% by weight, approximately 30% to approximately 40% by weight, approximately 40% to approximately 90% by weight, approximately 40% to approximately 80% by weight, approximately 40% to approximately 75% by weight, approximately 40% to approximately 70% by weight, approximately 40% to approximately 60% by weight, approximately 40% to approximately 50% by weight, approximately 50% to approximately 90% by weight, approximately 50% by weight About 80% by weight, about 50% to about 75% by weight, about 50% to about 70% by weight, about 50% to about 60% by weight, about 60% to about 90% by weight, about 60% to about 80% by weight %, about 60% to about 75%, about 60% to about 70%, about 70% to about 90%, about 70% to about 80%, about 80% to about 90%, about 9% by weight % to about 37%, about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, 95%, or 99% by weight of the oil FFA. By way of yet further example and without limitation, in any of the foregoing embodiments in which a minimum amount of MAG and / or DAG is not recited, the FFA can be present in up to about 100% of the oil.

[0057] In any of the foregoing embodiments, the oil may comprise 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, or substantially no triacylglycerols (TAGs). As a further example, the oil may have no measurable TAGs as qualitatively assessed by thin layer chromatography (TLC). In this method, the components of the oil are separated using a TLC plate (Analtech Uniplate silica gel GHL with inorganic binder, 20×20 cm, 250 μm) using a solvent (hexane:diethyl ether:acetic acid (70:30:1) solution. Typical sample size is 0.2 μL. After the solvent front reaches near the top of the plate (approximately 1 cm), the plate is removed from the TLC tank and the solvent is evaporated in a fume hood. The components are visualized with iodine vapor (at room temperature) in the TLC tank and relative intensity estimated by colorimetric imaging. The components can also be quantitatively measured by standard HPLC and GC / MS methods. As yet another example, the oil may have no measurable TAGs as assessed by gas chromatography (GC) or high performance liquid chromatography (HPLC). By way of example and not limitation, HPLC may be performed under the following HPLC conditions:C18 column, 4.6 mm ID x 250 mm, 5 um, column temperature at 30°C, charged aerosol detector, mobile phase A consisting of 75% acetonitrile, 12% methanol, 8% water, 4% tetrahydrofuran, and 0.3% acetic acid, mobile phase B consisting of 90% acetone and 10% acetonitrile, with the following gradient profile: 100% A at 1.5 mL / min from 0 to 5 min, 100% A from 5 to 11 min, 100% B at 1.5 mL / min from 0 to 5 min, 100% C at 1.5 mL / min from 5 to 11 min, using MAG, DAG, TAG and FFA calibration standards. 100% A to 96% A at 1.5 mL / min for 11-24 min, 96% A to 37% A at 1.5 mL / min for 11-24 min, 37% A to 32% A at 1.5 mL / min for 24-35 min, 32% A to 18% A at 1.5 mL / min for 35-45 min, 18% A to 15% A at 1.9 mL / min for 45-58 min, 15% A to 5% A at 1.9 mL / min for 58-60 min, 5% A to 100% A at 1.5 mL / min for 60-63 min, and 100% A at 1.5 mL / min for 63-65 min. Methods for quantitative measurement of glycerides and free fatty acids are described, by way of example and not limitation, in Simultaneous Analysis of Glycerides (Mono-, Di-, and Triglycerides) and Free Fatty Acids in Palm Oil, Application Note 1039, Thermo Fisher Scientific, Inc., 2012, Annex 5.

[0058] In any of the foregoing embodiments, the oil can contain two or more different fatty acids. By way of example and not limitation, the oil can contain 2, 3, 4, 5, or more different fatty acids.

[0059] In any of the foregoing embodiments, the free fatty acids comprising two or more different fatty acids may be selected from the group consisting of, by way of example and without limitation, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, heptadecenoic acid, stearic acid, nonadecylic acid, vaccenic acid, oleic acid, linoleic acid, linolenic acid, stearidonic acid, octadecatetraenoic acid, arachidic acid, heneicosylic acid, gondoic acid, eicosadienoic acid, paulic acid, behenic acid, tricosylic acid, erucic acid, lignoceric acid, docosahexaenoic acid, eicosapentenoic acid, nervonic acid, and isomers thereof. Alternatively, the fatty acids comprising two or more different fatty acids may each independently be selected from the group consisting of C6 fatty acids, such as, for example and not limited to, C6:0, C7 fatty acids, C8 fatty acids, such as, for example and not limited to, C8:0 fatty acids, C9 fatty acids, C10 fatty acids, C11 fatty acids, C12 fatty acids, C13 fatty acids, C14 fatty acids, C15 fatty acids, C16 fatty acids, C17 fatty acids, C18 fatty acids, such as, for example and not limited to, C18:0 fatty acids, C18:0 fatty acids, C18:1 fatty acids, C18:2 fatty acids, or C18:3 fatty acids, C19 fatty acids, C20 fatty acids, such as, for example and not limited to, C20:5 fatty acids, C21 fatty acids, C22 fatty acids, such as, for example and not limited to, C22:6 fatty acids, C23 fatty acids, and C24 fatty acids. As used herein, C18 should be understood to refer to stearic acid (C18:0).

[0060] In any of the foregoing embodiments, the oil may include non-oil components naturally occurring in the oil. By way of example and without limitation, non-oil components naturally occurring in the oil may include one or more of glycosphingolipids such as ceramide phosphate, glycoglycerolipids such as monogalactosyl diacylglycerol, phophatidyl alcohols such as phosphatidylmethanol, steroids such as sitosteryl esters, natural lipids such as campesterol esters, sphingolipids, phosphatidylglycerols, wax esters, sphingomyelins, phosphatides, plant sterols (campesterol, stigmasterol, sitosterol), cholesterol, tocopherols, tocotrienols, carotenes, xanthophylls, betaxanthins, chlorophyll, long chain alcohols, polyphenols, terpenes (cycloalanol, ... The present invention may include, for example, cycloarterenol, 24-methylenecycloarterenol, terpenoids (squalene), tocopherols, vitamins, paraffins, isothiocyanates, oxazolidinethiones, glucosinolates, sanguinarine, gossypol, glycosylated alkaloids, phospholipids, sphingosines, diacylglyceride ethers, glycolipids, phytic acid, quinic acid, oxalic acid, tartaric acid, anacardic acid, malic acid, caftaric acid, ctaranic acid, fertharic acid, phenylethanoids, hydroxycinnamic acids, phenolic acids, phytoestrogens, lignans, isoflavonoids, flavonoids, monoterpenes, diterpenes, triterpenoids, coenzymes, or combinations thereof. In any of the foregoing embodiments, the oil can include non-oil components that are derived and naturally occurring from the oil or oil source and are selected from the group consisting of α-tocopherol, β-tocopherol, δ-tocopherol, γ-tocopherol, α-tocotrienol, β-tocotrienol, δ-tocotrienol, and γ-tocotrienol.In any of the foregoing embodiments, the oil may comprise non-oil components that are derived from and naturally occurring in the oil source and are selected from the group consisting of ceramide phosphate, monoglactodiacylglycerol, phosphatidylmethanol, sitosteryl ester, campestrol ester, sphingolipid, phosphatidylglycerol, wax ester, sphingomyelin, and combinations thereof. It should be understood that the levels of the non-oil components may be the same as or greater than the levels in the oil source. By way of example and not limitation, the non-oil components may be determined by LC / MS / MS analysis.

[0061] In any of the foregoing embodiments, the oil can further comprise monoacylglycerol (MAG). By way of example and not limitation, MAG can comprise at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 40%, about 50%, about 60%, about 70%, about 75%, about 80%, or about 90% by weight of the total weight of the oil. Amount%, about 90% by weight, about 95% by weight, about 98% by weight, about 5% by weight - about 98% by weight, about 5% by weight - about 95% by weight, about 5% by weight - about 90% by weight, about 5% by weight - about 80% by weight, about 5% by weight - about 75% by weight, about 5% by weight - about 70% by weight, about 5% by weight - about 60% by weight, about 5% by weight Amount %~about 50 weight%, about 5 weight%~about 40 weight%, about 5 weight%~about 30 weight%, about 5 weight%~about 25 weight%, about 5 weight%~about 20 weight%, about 5 weight%~about 10 weight%, about 10 weight%~about 98 weight%, about 10 weight%~about 95 weight%, about 10 weight%~about 90 weight%, about 1 0% to approximately 80% by weight, approximately 10% to approximately 75% by weight, approximately 10% to approximately 70% by weight, approximately 10% to approximately 60% by weight, approximately 10% to approximately 50% by weight, approximately 10% to approximately 40% by weight, approximately 10% to approximately 30% by weight, approximately 10% to approximately 25% by weight, approximately 10% to approximately 20% by weight, approximately 20% by weight to approximately 98% by weight, approximately 20% to approximately 95% by weight, approximately 20% to approximately 90% by weight, approximately 20% to approximately 80% by weight, approximately 20% to approximately 75% by weight, approximately 20% to approximately 70% by weight, approximately 20% to approximately 60% by weight, approximately 20% to approximately 50% by weight, approximately 20% to about 40% by weight, about 20% to about 30% by weight, about 20% to about 25% by weight, about 25% to about 98% by weight, about 25% to about 95% by weight, about 25% to about 90% by weight, about 25% to about 80% by weight, about 25% to about 75% by weight, about 25% by weight About 70% by weight, about 25% to about 60% by weight, about 25% to about 50% by weight, about 25% to about 40% by weight, about 25% to about 30% by weight, about 30% to about 98% by weight, about 30% to about 95% by weight, about 30% to about 90% by weight, about 30% to about 80% by weight,Approximately 30% to approximately 75% by weight, approximately 30% to approximately 70% by weight, approximately 30% to approximately 60% by weight, approximately 30% to approximately 50% by weight, approximately 30% to approximately 40% by weight, approximately 40% by weight Amount %~about 98 weight%, about 40 weight%~about 95 weight%, about 40 weight%~about 90 weight%, about 40 weight%~about 80 weight%, about 40 weight%~about 75 weight%, about 40 weight%~about 70% by weight, about 40% to about 60% by weight, about 40% to about 50% by weight, about 50% to about 98% by weight, about 50% to about 95% by weight, about 50% to about 90% by weight %, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 60%, about 60% to about 98%, about 6 0% to approximately 95% by weight, approximately 60% to approximately 90% by weight, approximately 60% to approximately 80% by weight, approximately 60% to approximately 75% by weight, approximately 60% to approximately 70% by weight, approximately 70% by weight ~98% by weight, approximately 70% by weight ~ approximately 95% by weight, approximately 70% by weight ~ approximately 90% by weight, approximately 70% by weight ~ approximately 80% by weight, approximately 70% by weight ~ approximately 75% by weight, approximately 75% by weight ~ approximately 98 %, about 75% to about 95% by weight, about 75% to about 90% by weight, about 75% to about 80% by weight, about 80% to about 98% by weight, about 80% to about 95% by weight, about 80% to about 90% by weight, about 80% to about 90% by weight, about 90% to about 98% by weight, about 90% to about 95% by weight, or about 95% to about 98% by weight. In any of the foregoing embodiments, the oil can further comprise diacylglycerol (DAG). By way of example, and without limitation, DAG may be present in an amount greater than about 5 wt.%, between about 5 wt.% and about 66 wt.%, between about 10 wt.% and about 66 wt.%, between about 20 wt.% and about 66 wt.%, between about 30 wt.% and about 66 wt.%, between about 30 wt.% and about 66 wt.%, between about 40 wt.% and about 66 wt.%, between about 50 wt.% and about 50 wt.%, between about 10 wt.% and about 50 wt.%, between about 20 wt.% and about 50 wt.%, between about 30 wt.% and about 5 wt.%, 0% by weight, about 40% by weight to about 50% by weight, about 5% by weight to about 40% by weight, about 10% by weight to about 40% by weight, about 20% by weight to about 40% by weight, about 30% by weight to about 40% by weight, about 5% by weight to about 30% by weight, about 10% by weight to about 30% by weight, about 20% by weight to about 30% by weight, about 5% by weight to about 20% by weight, about 10% by weight to about 20% by weight, about 5% by weight to about 10% by weight, or about 5%, 10%, 15%, 20%,The oil may be present in an amount of 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or 66% by weight. Alternatively, in any of the above embodiments, the oil may further comprise MAG and DAG. By way of example and not limitation, MAG and DAG may be present in an amount of at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 9 ... About 60% by weight, about 70% by weight, about 75% by weight, about 80% by weight, about 90% by weight, about 95% by weight, about 98% by weight, about 5% by weight - about 98% by weight, about 5% by weight - about 95% by weight, about 5% by weight - about 90% by weight, about 5% by weight - about 80% by weight, about 5% by weight - about 75% by weight, about 5% to about 70% by weight, about 5% to about 60% by weight, about 5% to about 50% by weight, about 5% to about 40% by weight, about 5% to about 30% by weight, about 5% to about 25% by weight, about 5% to about 20% by weight, about 5% to about 10% by weight , about 10% to about 98% by weight, about 10% to about 95% by weight, about 10% to about 90% by weight, about 10% to about 80% by weight, about 10% to about 75% by weight, about 10% to about 70% by weight, about 10% to about 60% by weight, about 10% to about 5 0% by weight, about 10% to about 40% by weight, about 10% to about 30% by weight, about 10% to about 25% by weight, about 10% to about 20% by weight, about 20% to about 98% by weight, about 20% to about 95% by weight, about 20% to about 90% by weight, about 20% by weight ~80% by weight, approximately 20% by weight ~ approximately 75% by weight, approximately 20% by weight ~ approximately 70% by weight, approximately 20% by weight ~ approximately 60% by weight, approximately 20% by weight ~ approximately 50% by weight, approximately 20% by weight ~ approximately 40% by weight, approximately 20% by weight ~ approximately 30% by weight, approximately 20% by weight ~ approximately 25% by weight, approximately 25 Weight% to about 98% by weight, about 25% to about 95% by weight, about 25% to about 90% by weight, about 25% to about 80% by weight, about 25% to about 75% by weight, about 25% to about 70% by weight, about 25% to about 60% by weight, about 25% to about 50% by weight,About 25% to about 40% by weight, about 25% to about 30% by weight, about 30% to about 98% by weight, about 30% to about 95% by weight, about 30% to about 90% by weight, about 30% to about 80% by weight, Approximately 30% to approximately 75% by weight, approximately 30% to approximately 70% by weight, approximately 30% to approximately 60% by weight, approximately 30% to approximately 50% by weight, approximately 30% to approximately 40% by weight, approximately 40% to approximately 98% by weight, approximately 40% to approximately 95% by weight, approximately 40% to approximately 90% by weight, approximately 40% to approximately 80% by weight, approximately 40% to approximately 75% by weight, approximately 40% to approximately 70% by weight, approximately 40% to approximately 60% by weight, approximately 40% to about 50% by weight, about 50% to about 98% by weight, about 50% to about 95% by weight, about 50% to about 90% by weight, about 50% to about 80% by weight, about 50% to about 75% by weight, about 5 0% to approximately 70% by weight, approximately 50% to approximately 60% by weight, approximately 60% to approximately 98% by weight, approximately 60% to approximately 95% by weight, approximately 60% to approximately 90% by weight, approximately 60% to approximately 80% by weight, approximately 6 0% to about 75% by weight, about 60% to about 70% by weight, about 70% to about 98% by weight, about 70% to about 95% by weight, about 70% to about 90% by weight, about 70% to about 80% by weight, about 70 It can be present in the oil in an amount of about 75% by weight to about 75% by weight, about 75% by weight to about 98% by weight, about 75% by weight to about 95% by weight, about 75% by weight to about 90% by weight, about 75% by weight to about 80% by weight, about 80% by weight to about 98% by weight, about 80% by weight to about 95% by weight, about 80% by weight to about 90% by weight, about 90% by weight to about 98% by weight, about 90% by weight to about 95% by weight, or about 95% by weight to about 98% by weight.

[0062] In any of the foregoing embodiments, the FFAs may be present based on the weight percent of the MAG, or vice versa, where applicable. In any of the foregoing embodiments, the combination of MAG and FFAs may be from about 60% to about 95% by weight of the total weight of the oil. By way of example, and without limitation, the total combination of MAGs and FFAs may be about 60% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, about 90% to about 95% by weight, about 60% to about 90% by weight, about 70% to about 90% by weight, about 75% to about 90% by weight, about 80% to about 90% by weight, about 60% to about 80% by weight, about 70% to about 80% by weight, about 75% to about 80% by weight, about 60% to about 75% by weight, about 70% to about 75% by weight, about 60% to about 70% by weight, or about 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% by weight of the total weight of the oil.

[0063] In any of the foregoing embodiments, the MAG in the oil can have a ratio of sn-1 substitutions to sn-2 substitutions of greater than 1. By way of example and not limitation, the MAG in the oil can have a ratio of sn-1 substitutions to sn-2 substitutions of greater than 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, or 100.

[0064] In any of the foregoing embodiments, the oil may have a fatty acid profile that includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 of C6:0, C8:0, C10, C12, C14, C16, C18, C18:1, C18:2, C18:3, C20, and C22, each fatty acid ranging from about 0.1% to 85% of the total fatty acid content. By way of example and not limitation, for each fatty acid, the amount may be from about 0.1% to about 85%, from about 0.5% to about 85%, from about 1% to about 85%, from about 2% to about 85%, from about 3% to about 85%, from about 4% to about 85%, from about 5% to about 85%, from about 10% to about 85%, from about 15% to about 85%, from about 20% to about 85%, from about 25% to about 85%, from about 30% to about 85%, from about 35% to about 85%, from about 40% of the total fatty acid content. ~ about 85%, about 45% to about 85%, about 50% to about 85%, about 55% to about 85%, about 60% to about 85%, about 65% to about 85%, about 70% to about 85%, about 75% to about 85%, about 80% to about 85%, about 0.1% to about 80%, about 0.5% to about 80%, about 1% to about 80%, about 2% to about 80%, about 3% to about 80%, about 4% to about 80%, about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 18% to about 80%, about 20% to about 80%, about 25% to about 80%, about 26% to about 80%, about 27% to about 80%, about 28% to about 80%, about 29% to about 80%, about 30% to about 80%, about 31% to about 80%, about 32% to about 80%, about 33% to about 80%, about 34% to about 80%, about 35% to about 80%, about 36% to about 80%, about 37% to about 80%, about 38% to about 80%, about 39 ... About 80%, about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, about 0.1% to about 75%, about 0.5% to about 75%, about 1% to about 75%, about 2% to about 75%, about 3% ~ about 75%, about 4% to about 75%, about 5% to about 75%, about 10% to about 75%, about 15% to about 75%, about 20% to about 75%, about 25% to about 75%, about 30% to about 75%, about 35% to about 75%, about 40% to about 75%, about 45% to about 75%, about 50% to about 75%, about 55% to about 75%, about 60% to about 75%, about 65% to about 75%, about 70% to about 75%, about 0.1% to about 70%, about 0.5% to about 70%, about 1% to about 70%, about 2% to about 70%, about 3% to about 70%, about 4% to about 70%, about 5% to about 70%, about 10% to about 70%, about 15% to about 70%, about 20% to about 70%, about 25% to about 70%, about 30% to about 70%, about 35% to about 70%, about 40% to about 70%, about 45% to about 70%, about 50% to about 70%, about 55% to about 70%, about 60% to about 70%, about 65% to about 70%, about 0.1% to about 65%, about 0.5% to about 65%, about 1% to about 65%, about 2% to about 65%, about 3% to about 65%, about 4% to about 65%, about 5% to about 65%, about 10 % to about 65%, about 15% to about 65%, about 20% to about 65%, about 25% to about 65%, about 30% to about 65%, about 35% to about 65%, about 40% to about 65%, about 45% to about 65%, about 50% to about 65%, about 55% to about 65%, about 60% to about 65%, about 0.1% to about 60%, about 0.5% to about 60%, about 1% to about 60%, about 2% to about 60%, about 3% to about 60%, about 4% to about 60%, about 5% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 40% to about 60% , about 45% to about 60%, about 50% to about 60%, about 55% to about 60%, about 0.1% to about 55%, about 0.5% to about 55%, about 1% to about 55%, about 2% to about 55%, about 3% to about 55%, about 4% to about 55%, about 5% to about 55%, about 10% to about 55%, about 15% to about 55%, about 20% to about 55%, about 25% to about 55%, about 30% to about 55%, about 35% to about 55%, about 40% to about 55%, about 45% to about 55%, about 50% to about 55%, about 0.1% to about 50%, about 0.5% to about 50%, about 1% to about 50%, about 2% to about 50%, about 3% to about 50%, about 4% to about 5 0%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50%, about 45% to about 50%, about 0.1% to about 45%, about 0.5% to about 45%, about 1% to about 45%, about 2% to about 45%, about 3% to about 45%, about 4% to about 45%, about 5% to about 45%, about 10% to about 45%, about 15% to about 45%, about 20% to about 45%, about 25% to about 45%, about 30% to about 45%, about 35% to about 45%, about 40% to about 45%, about 0.1% to about 40%, about 0.5% to about 40%, about 1% to about 40%, about 2% to about 40%, about 3% to about 40%, about 4% to about 40%, about 5% to about 40%, about 10% to about 40%, about 15% to about 40%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 35% to about 40%, about 0.1% to about 35% , about 0.5% to about 35%, about 1% to about 35%, about 2% to about 35%, about 3% to about 35%, about 4% to about 35%, about 5% to about 35%, about 10% to about 35%, about 15% to about 35%, about 20% to about 35%, about 25% to about 35%, about 30% to about 35%, about 0.1% to about 30%, about 0.5% ~ about 30%, about 1% to about 30%, about 2% to about 30%, about 3% to about 30%, about 4% to about 30%, about 5% to about 30%, about 10% to about 30%, about 15% to about 30%, about 20% to about 30%, about 25% to about 30%, about 0.1% to about 25%, about 0.5% to about 25%, about 1% to about 25%, about 2% to about 25%, about 3% to about 25%, about 4% to about 25%, about 5% to about 25%, about 10% to about 25%, about 15% to about 25%, about 20% to about 25%, about 0.1% to about 20%, about 0.5% to about 20%, about 1% to about 20%, about 2% to about 20%, about 3% to about 20%, about 4% to about 20%, about 5% to about 20%, about 10% to about 20%, about 15% to about 20%, about 0.1% to about 15%, about 0.5% to about 15%, about 1% to about 15%, about 2% to about 15%, about 3% to about 15%, about 4% to about 15%, about 5% to about 15%, about 10% to about 15%, about 0.1% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 0.1% to about 5%, about 0.5% to about 5%, about 1% to about 5%, about 2% to about 5%, about 3% to about 5%, about 4% to about 5%, about 0.1% to about 4%, about 0.5% to about 4%, about 1% It may be about 4%, about 2% to about 4%, about 3% to about 4%, about 0.1% to about 3%, about 0.5% to about 3%, about 1% to about 3%, about 2% to about 3%, about 0.1% to about 2%, about 0.5% to about 2%, about 1% to about 2%, about 0.1% to about 1%, about 0.5% to about 1%, or about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% or 85%.

[0065] As an example, and not by way of limitation, when the oil is derived from linseed oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 10% to about 20%, C18:2 in an amount of about 10% to about 20%, and C18:3 in an amount of about 50% to about 65%.

[0066] As an example, and not by way of limitation, when the oil is derived from MCT oil, the two or more different fatty acids can include two or more fatty acids derived from C8:0 in an amount of about 50% to about 65% of the total fatty acid content of the oil, and C10 in an amount of about 35% to about 50% of the total fatty acid content of the oil.

[0067] By way of example, and not limitation, when the oil is derived from rosehip oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 15% to about 25% of the total fatty acid content of the oil, C18:2 in an amount of about 45% to about 55% of the total fatty acid content of the oil, and C18:3 in an amount of about 15% to about 25% of the total fatty acid content of the oil.

[0068] As an example, and not by way of limitation, when the oil is derived from sesame oil, the two or more different fatty acids can include two or more fatty acids derived from C18 in an amount of about 10% to about 20% of the total fatty acid content of the oil, C18:1 in an amount of about 35% to about 45% of the total fatty acid content, and C18:2 in an amount of about 30% to about 45% of the total fatty acid content.

[0069] By way of example, and not limitation, when the oil is derived from hemp seed oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 5% to about 20% of the total fatty acid content of the oil, C18:2 in an amount of about 50% to about 65% of the total fatty acid content, and C18:3 in an amount of about 15% to about 25% of the total fatty acid content.

[0070] As an example, and not by way of limitation, when the oil is derived from sunflower oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 15% to about 25% of the total fatty acid content of the oil, and C18:2 in an amount of about 60% to about 80% of the total fatty acid content.

[0071] As an example, and not by way of limitation, when the oil is derived from canola oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 55% to about 70% of the total fatty acid content of the oil, and C18:2 in an amount of about 15% to about 30% of the total fatty acid content.

[0072] As an example, and not by way of limitation, when the oil is derived from almond oil, the two or more different fatty acids can include two or more fatty acids: C18:1 in an amount of about 60% to about 80% of the total fatty acid content of the oil, and C18:2 in an amount of about 10% to about 25% of the total fatty acid content of the oil.

[0073] By way of example, and not limitation, when the oil is derived from olive oil, the two or more different fatty acids can include two or more fatty acids derived from C16 in an amount between about 5% and about 20% of the total fatty acid content of the oil, C18:1 in an amount between about 65% and about 80% of the total fatty acid content, and C18:2 in an amount between about 5% and about 15% of the total fatty acid content.

[0074] By way of example, and not limitation, when the oil is derived from oat oil, the two or more different fatty acids can include two or more fatty acids derived from C16 in an amount of about 5% to about 20% of the total fatty acid content of the oil, C18:1 in an amount of about 15% to about 30% of the total fatty acid content, and C18:2 in an amount of about 45% to about 60% of the total fatty acid content.

[0075] The oils described herein, including those used to produce the EMOs, FFAs, and nanoemulsions of the present disclosure, can be MCT oils containing about 55-65% C8, 35-45% C10, and about 0% to about 10% of different chain lengths, but preferably no more than 2% of other chain lengths.

[0076] In any of the foregoing embodiments, the droplets or particles can have an average zeta potential of less than about -30 mV. By way of example and not limitation, the droplets or particles can have an average zeta potential of less than about -35 mV, less than about -40 mV, less than about -45 mV, less than about -50 mV, less than about -60 mV, less than about -70 mV, between about -30 mV and about -80 mV, between about -30 mV and about -75 mV, between about -30 mV and about -70 mV, between about -30 mV and about -60 mV, between about -30 mV and about -50 mV, between about -30 mV and about -40 mV, between about -40 mV and about -80 mV, between about -40 mV and about -75 mV, between about -40 mV and about -70 mV, between about -40 mV and about -60 mV, The average zeta potential may be about -40mV to about -50mV, about -50mV to about -80mV, about -50mV to about -75mV, about -50mV to about -70mV, about -50mV to about -60mV, about -60mV to about -80mV, about -60mV to about -75mV, about -60mV to about -70mV, about -70mV to about -80mV, about -70mV to about -75mV, about -30mV, -35mV, -40mV, -45mV, -50mV, -60mV, -70mV, -75mV, or -90mV. In certain embodiments, the zeta potential may be measured by electrophoretic light scattering.

[0077] In any of the foregoing embodiments, the droplets or particles can have a polydispersity index (PDI) of less than about 0.3. By way of example and without limitation, the droplets or particles can have a PDI of less than about 0.3, less than about 0.25, less than about 0.2, less than about 0.175, about 0.15 to about 0.3, about 0.2 to about 0.3, about 0.25 to about 0.3, about 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, or 0.3. In certain aspects, the PDI can be measured by dynamic light scattering.

[0078] In any of the foregoing embodiments, the droplets or particles can have a Z-average size of about 300 nm or less. By way of example and not limitation, the droplets or particles can be about 300 nm or less, about 275 nm or less, about 250 nm or less, about 225 nm or less, about 200 nm or less, about 175 nm or less, about 150 nm or less, about 100 nm to about 300 nm, about 100 nm to about 250 nm, about 100 nm to about 200 nm, about 150 nm to about 300 nm, about 150 nm to about 250 nm, about 150 nm to about 200 nm, about 200 nm to about 300 nm. , about 200 nm to about 250 nm, about 250 nm to about 300 nm, about 150 nm, about 160 nm, about 170 nm, about 175 nm, about 180 nm, about 190 nm, about 200 nm, about 210 nm, about 220 nm, about 225 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 275 nm, about 280 nm, about 290 nm, or about 300 nm. In certain embodiments, the Z-average size can be measured by dynamic light scattering.

[0079] In any of the foregoing embodiments, the oil may comprise a processed oil from an oil source that has been subjected to an enzymatic treatment selected from the group consisting of enzymatic hydrolysis to obtain free fatty acids and glycerol, with removal of glycerol to obtain a FFA oil, enzymatic re-esterification of FFAs to obtain monoacylglycerol (MAG) and free fatty acids, and optionally diacylglycerol (DAG), and both enzymatic hydrolysis to obtain free fatty acids and glycerol, with removal of glycerol to obtain a FFA oil, and enzymatic re-esterification of FFAs to obtain monoacylglycerol (MAG) and free fatty acids, and optionally diacylglycerol (DAG). By way of example and not limitation, the oil or a portion thereof may be an enzyme modified oil (EMO) that has been subjected to enzymatic hydrolysis to obtain free fatty acids and glycerol, separation of glycerol from the free fatty acid oil, and subsequent enzymatic re-esterification to obtain monoacylglycerol, free fatty acids, and optionally diacylglycerol. It should be understood that the oil so treated can be from a single oil source or a combination of oil sources subjected to enzyme treatment. It should further be understood that EMO and / or FFA oils from a single or multiple oil sources can be blended after enzyme treatment to formulate the oil in the composition of the present disclosure. Thus, in some embodiments, the oil can comprise a blend of EMO and FFA oils from one, two, three, four, five or more oil sources. It should also be understood that the EMO and / or FFA oil can be blended with unmodified TAG oil to obtain the oil in the composition of the present disclosure. Thus, in some embodiments, the oil can comprise a blend of two or more processed oils from each of a first oil source and a second oil source. By way of example and not limitation, the oil can comprise a blend of two, three, four or more processed oils.

[0080] Thus, in some embodiments, the MAG and optionally the DAG in the composition, or a portion thereof, can be derived from a first oil source. In further embodiments, the FFA, or a portion thereof, can be derived from a second oil source. In other embodiments, the FFA, or a portion thereof, can be derived from the same oil source as the first oil source. It should be understood that various combinations of MAG, DAG, TAG, and FFA from different oils can be used. In any of the above embodiments, the oil can be derived from a single oil source, two oil sources, three oil sources, four oil sources, five or more oil sources.

[0081] In any of the foregoing embodiments, the MAG can include two or more different MAGs. By way of example and not limitation, the MAG can include two, three, four, five, or more different MAGs. By way of further example and not limitation, the MAG can be selected from the group consisting of monocaproin, monocaprylin, monocaprin, monolaurin, monomyristin, monopalmitin, monostearin, monoolein, monolinolein, monolinolenin, monoeicosapentaenoin, monodocosahexaenoin, and combinations thereof.

[0082] The oil may be from a single oil source and type, such as, for example and without limitation, EMO from a single oil source, but as noted, the oil may contain components from multiple oil sources. For example and without limitation, the oil may contain EMO from a first oil source and FFA oil from a second oil source. For a further example and without limitation, the oil may contain a first EMO from a first oil source and a second EMO from a second oil source. For a further example and without limitation, the oil may contain a first EMO from a first oil source, a second EMO from a second oil source, and a FFA oil from a third oil source. Thus, it should be understood that any combination of oil components from oil sources used to form the nanoemulsions of the present disclosure is within the scope of the present disclosure, even unmodified TAG oil. For a further example and without limitation, when EMO is used, the EMO may be from two or more oil sources. It should be understood that when the first oil source is EMO, at least a portion of the FFA in the composition may be from EMO and the first oil source.

[0083] In any of the foregoing embodiments, the oil or portion thereof, such as, by way of example and not limitation, EMO and / or FFA oil, may be derived from an oil source selected from plant, animal, fish, algae oils, and combinations thereof. In any of the foregoing embodiments, by way of example and not limitation, the oil can be derived from olive oil, almond oil, canola oil, coconut oil, cottonseed oil, palm kernel oil, palm olein oil, palm stearin oil, peanut oil, linseed oil, sunflower seed oil, corn oil, grapeseed oil, pomegranate oil, rosehip oil, hemp seed oil, prickly pear oil, medium chain fatty acid oil, safflower oil, sesame oil, walnut oil, palm oil, soybean oil, fish oil, sardine oil, anchovy oil, algae oil, chicken fat, lard, krill oil, avocado oil, mustard oil, rice bran oil, oat oil, nutmeg butter, macadamia nut oil, cocoa butter, rapeseed oil, poppy seed oil, castor oil, edible oils, medicinal oils, and combinations thereof. By way of example and without limitation, first and second oil sources may be utilized that may be derived from olive oil, almond oil, canola oil, coconut oil, cottonseed oil, palm kernel oil, palm olein oil, palm stearin oil, peanut oil, linseed oil, sunflower seed oil, corn oil, grapeseed oil, pomegranate oil, rosehip oil, hemp seed oil, prickly pear oil, medium chain fatty acid oil, safflower oil, sesame oil, walnut oil, palm oil, soybean oil, fish oil, sardine oil, anchovy oil, algae oil, chicken fat, lard, krill oil, avocado oil, mustard oil, rice bran oil, oat oil, nutmeg butter, macadamia nut oil, cocoa butter, rapeseed oil, poppy seed oil, castor oil, edible oils, medicinal oils, and combinations thereof. It should be further understood that the oil of the compositions of the present disclosure can include two, three, four or more oils derived from different crude oils.

[0084] In some embodiments, the oil can include an unmodified TAG oil component. The TAG oil component can be an oil selected from plant, animal, fish, algae oils, and combinations thereof. By way of example, and without limitation, the unmodified TAG oil component can be olive oil, almond oil, canola oil, coconut oil, cottonseed oil, palm kernel oil, palm olein oil, palm stearin oil, peanut oil, linseed oil, sunflower seed oil, corn oil, grapeseed oil, pomegranate oil, rosehip oil, hemp seed oil, prickly pear oil, medium chain fatty acid oil, safflower oil, sesame oil, walnut oil, palm oil, soybean oil, fish oil, sardine oil, anchovy oil, algae oil, chicken fat, lard, krill oil, avocado oil, mustard oil, rice bran oil, oat oil, nutmeg butter, macadamia nut oil, cocoa butter, rapeseed oil, poppy seed oil, castor oil, edible oils, medicinal oils, and combinations thereof. By way of example and without limitation, first and second oil sources may be utilized that may be derived from olive oil, almond oil, canola oil, coconut oil, cottonseed oil, palm kernel oil, palm olein oil, palm stearin oil, peanut oil, linseed oil, sunflower seed oil, corn oil, grapeseed oil, pomegranate oil, rosehip oil, hemp seed oil, prickly pear oil, medium chain fatty acid oil, safflower oil, sesame oil, walnut oil, palm oil, soybean oil, fish oil, sardine oil, anchovy oil, algae oil, chicken fat, lard, krill oil, avocado oil, mustard oil, rice bran oil, oat oil, nutmeg butter, macadamia nut oil, cocoa butter, rapeseed oil, poppy seed oil, castor oil, edible oils, medicinal oils, and combinations thereof. It is further understood that the oil of the compositions of the present disclosure can include two, three, four or more oils from various oil sources. In any of the foregoing embodiments, the TAG oil component can be present in up to 80% by weight of the oil.By way of example, and not limitation, the TAG oil component may be from about 0.1% to about 80% by weight, from about 1% to about 80% by weight, from about 5% to about 80% by weight, from about 10% to about 80% by weight, from about 20% to about 80% by weight, from about 30% to about 80% by weight, from about 40% to about 80% by weight, from about 50% to about 80% by weight, from about 60% to about 80% by weight, from about 70% to about 80% by weight, from about 0.1% to about 70% by weight, from about 1% to about 70% by weight, from about 5% to about 70% by weight, from about 10% to about 70% by weight, from about 2 ... 0% by weight, about 30% to about 70% by weight, about 40% to about 70% by weight, about 50% to about 70% by weight, about 60% to about 70% by weight, about 0.1% to about 60% by weight, about 1% to about 60% by weight, about 5% to about 60% by weight, about 10% to about 60% by weight %, about 20% to about 60% by weight, about 30% to about 60% by weight, about 40% to about 60% by weight, about 50% to about 60% by weight, about 0.1% to about 50% by weight, about 1% to about 50% by weight, about 5% to about 50% by weight, about 10% to about 50% by weight, about 2 0% to about 50% by weight, about 30% to about 50% by weight, about 40% to about 50% by weight, about 0.1% to about 40% by weight, about 1% to about 40% by weight, about 5% to about 40% by weight, about 10% to about 40% by weight, about 20% to about 40% by weight, about 30% to Approximately 40% by weight, approximately 0.1% to approximately 30% by weight, approximately 1% to approximately 30% by weight, approximately 5% to approximately 30% by weight, approximately 10% to approximately 30% by weight, approximately 20% to approximately 30% by weight, approximately 0.1% to approximately 20% by weight, approximately 1% to approximately 20% by weight, approximately 5% to approximately 20% by weight The oil may be present in an amount of about 10% to about 20% by weight, about 0.1% to about 10% by weight, about 1% to about 10% by weight, about 5% to about 10% by weight, about 0.1% to about 5% by weight, about 1% to about 5% by weight, about 0.1% to about 1% by weight, or about 0.1%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, or about 80% by weight of the oil.

[0085] In any of the above embodiments, the oil may comprise a fatty acid profile that is within about 10% of the fatty acid profile from the oil source used to obtain the oil for at least one, two, or more fatty acids. In aspects in which two or more oil sources are used to form the oil, the fatty acid profile may be within about 10% of the fatty acid profile from the oil source according to the respective amounts of each oil source used to form the oil for at least one, two, or more fatty acids. By way of example, and without limitation, the fatty acid profile of the oil for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more fatty acids may be within 10% of the fatty acid profile for the same fatty acid in the oil source according to the respective amounts of each oil source used to form the oil when two or more oil sources are used, or for the oil source when only one oil source is used to form the oil. By way of further example, and without limitation, the fatty acid profile may be within about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% for each fatty acid in the oil compared to the oil source. For example, if the first oil source has 15% C18 fatty acids, the EMO can have about 5-25%, 6-24%, 7-23%, 8-22%, 9-21%, 10-20%, 11-19%, 12-18%, 13-17%, 14-16%, or about 15% C18 fatty acids. It should be understood that if the oil is a blend of EMO and FFA oils from different sources, the amount of fatty acids will vary according to the ratio of EMO and FFA oils, as well as the starting fatty acid profile. Exemplary fatty acid profiles are provided in the table below, which also includes an exemplary EMO composition based on experimental data. It should be understood that for the fatty acid profile, the amount of fatty acids can naturally vary by about 3-5%, depending on the species, growth conditions, and other variables. It should be understood that the expected fatty acid profile can be estimated based on the known fatty acid profile and the amount of EMO and / or FFA oil in the oil. [Table 1-1] [Table 1-2]

[0086] In any of the foregoing embodiments, the oil may be about 0.001% to about 90% by weight of the total weight of the composition. By way of example and not limitation, the oil may be about 0.001% to about 90% by weight, about 0.01% to about 90% by weight, about 0.1% to about 90% by weight, about 1% to about 90% by weight, about 2% to about 90% by weight, about 3% to about 90% by weight, about 4% to about 90% by weight, about 5% to about 90% by weight, about 10% to about 90% by weight, about 20% to about 90% by weight, about 30% to about 90% by weight, about 40% to about 90% by weight, about 50% to about 90% by weight, about 60% by weight, or the like. ~90% by weight, approximately 70% by weight ~ approximately 90% by weight, approximately 80% by weight ~ approximately 90% by weight, approximately 0.001% by weight ~ approximately 80% by weight, approximately 0.01% by weight ~ approximately 80% by weight, approximately 0.1% by weight ~ approximately 80% by weight, approximately 1% by weight ~ approximately 80% by weight, approximately 2% by weight ~ approximately 80% by weight %, about 3% to about 80%, about 4% to about 80%, about 5% to about 80%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80% by weight Amount%, about 60% to about 80% by weight, about 70% to about 80% by weight, about 0.001% to about 70% by weight, about 0.01% to about 70% by weight, about 1% to about 70% by weight, about 2% to about 70% by weight, about 3% to about 70% by weight, about 4% by weight ~70% by weight, approximately 5% to approximately 70% by weight, approximately 10% to approximately 70%, approximately 20% to approximately 70%, approximately 30% to approximately 70%, approximately 40% to approximately 70%, approximately 50% to approximately 70%, approximately 60% to approximately 70%, approximately 0. 001% by weight to approximately 60% by weight, approximately 0.01% to approximately 60% by weight, approximately 0.1% to approximately 60% by weight, approximately 1% to approximately 60% by weight, approximately 2% to approximately 60% by weight, approximately 3% to approximately 60% by weight, approximately 4% to approximately 60% by weight, approximately 5% to approximately 60% by weight %, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 0.001% to about 50%, about 0.01% to about 50%, about 0.1 wt % to about 50 wt %, about 1 wt % to about 50 wt %, about 2 wt % to about 50 wt %, about 3 wt % to about 50 wt %, about 4 wt % to about 50 wt %, about 5 wt % to about 50 wt %, about 10 wt % to about 50 wt %, about 20 wt % to about 50 wt %, about 30 wt % to about 50 wt %, about 30 wt % to about 50 wt %, about 0.001 wt % to about 40 wt %, about 0.01 wt % to about 40 wt %, about 0.1 wt % to about 40 wt %, about 1 wt % to about 40 wt %, about 2 wt % to about 40 wt %, about 3 wt % to about 40 wt %, about 4 wt % to about 40 wt %, about 5 % to about 40% by weight, about 10% to about 40% by weight, about 20% to about 40% by weight, about 30% to about 40% by weight, about 0.001% to about 30% by weight, about 0.01% to about 30% by weight, about 0.1% to about 30% by weight, about 1% to about 30% by weight, about 2% to about 30% by weight, about 3% to about 30% by weight, about 4% to about 30% by weight, about 5% to about 30% by weight, about 10% to about 30% by weight, about 20% to about 30% by weight, about 0.001% to about 20% by weight, about 0.01% to about 20% by weight, about 0.1% by weight to about 20% by weight, about 1% to about 20% by weight, about 2% to about 20% by weight, about 3% to about 20% by weight, about 4% to about 20% by weight, about 5% to about 20% by weight, about 10% to about 20% by weight, about 0.001% to about 15% by weight, about 0.01% to about 15% by weight, about 0.1% to about 15% by weight, about 1% to about 15% by weight, about 2% to about 15% by weight, about 3% to about 15% by weight, about 4% to about 15% by weight, about 5% to about 15% by weight, about 6% to about 15% by weight, about 7% to about 15% by weight, about 8% to about 1 5 wt%, about 9 wt% to about 5 wt%, about 10 wt% to about 15 wt%, about 11 wt% to about 15 wt%, about 12 wt% to about 15 wt%, about 13 wt% to about 15 wt%, about 14 wt% to about 15 wt%, about 0.001 wt% to about 10 wt%, about 0.01 wt% to about 10 wt%, about 0.1 wt% to about 10 wt%, about 1 wt% to about 10 wt%, about 2 wt% to about 10 wt%, about 3 wt% to about 10 wt%, about 4 wt% to about 10 wt%, about 5 wt% to about 10 wt%, about 0.001 wt% to about 5 wt%, about 0.01 wt% to about 5 wt%, about 0.It may be 1% by weight to about 5% by weight, about 1% by weight to about 5% by weight, about 2% by weight to about 10% by weight, about 2% by weight to about 5% by weight, about 3% by weight to about 10% by weight, about 3% by weight to about 5% by weight, about 4% by weight to about 10% by weight, about 4% by weight to about 5% by weight, about 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 15% by weight, 20% by weight, 25% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 75% by weight, 80% by weight, or 90% by weight.

[0087] In any of the foregoing embodiments, the liquid may be water or any suitable polar medium. By way of example and without limitation, the polar medium may be water, deionized water, saline, buffered water (e.g., phosphate buffered saline (PBS), citrate buffer, sodium acetate buffer), salt solutions (e.g., sodium chloride or potassium chloride), and other non-aqueous solutions.

[0088] In any of the foregoing embodiments, the Z-average size of the droplets or particles does not change by more than 15% over a period of at least 14 days when stored at room temperature (22° C.). By way of example and not limitation, the Z-average size of the droplets or particles does not change by more than 15% over a period of at least 14 days, 21 days, or 28 days when stored at room temperature (22° C.). By way of further example and not limitation, the Z-average size of the droplets or particles does not change by more than 15%, more than 10%, or more than 5% over a period of at least 14 days, 21 days, or 28 days when stored at room temperature (22° C.).

[0089] In any of the foregoing embodiments, the Z-average size of the droplets or particles does not change by more than 15% over a period of at least 14 days when stored at 4° C. By way of example and not limitation, the Z-average size of the droplets or particles does not change by more than 15% over a period of at least 14 days, 21 days, or 28 days when stored at 4° C. By way of further example and not limitation, the Z-average size of the droplets or particles does not change by more than 15%, more than 10%, or more than 5% over a period of at least 14 days, 21 days, or 28 days when stored at 4° C.

[0090] In any of the above embodiments, the oil may be in the form of droplets. Alternatively, in any of the above embodiments, the oil may be in the form of particles. For example, when the nanoemulsion is a solid lipid nanoemulsion (SLN), the oil is in the form of particles. It should be understood that droplets refer to liquid droplets and particles refer to solid particles.

[0091] In any of the above embodiments, the composition cannot include any exogenous additives having surfactant and / or emulsifier properties that are not naturally present in oil in an amount sufficient to enhance the stability of the droplets or particles.By way of example and without limitation, the composition cannot include polysorbates, phospholipids, sterols, cationic lipids, poloxamers, sorbitan esters, sugar esters, polyoxyethylene conjugates, phosphatidyl lapsidate ammonium, polyphenols, polyvinyl alcohol, lecithin, ethanol, lysophospholipids, ceramides, tweens, spans, corifol, propylene glycol, vitamin D, polyethylene glycol, polyethylene glycol derivatives, gum acacia, modified gum acacia, agar, ghatti gum, modified ghatti gum, pectin, carrageenan, xanthan gum, modified starch, modified alginate, fatty alcohols, ethoxylated polyols, and combinations thereof.

[0092] In any of the foregoing embodiments, the composition cannot include any exogenous additives that have thickening or crystallization-inhibiting properties that are not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively. By way of example and not limitation, the composition cannot include methylcellulose, corn starch, sodium alginate, or gelatin. By way of further example and not limitation, the composition cannot include polyglycerol fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, and combinations thereof. In certain aspects, the composition cannot include any exogenous additives that have thickening properties that are not naturally occurring in oils in amounts sufficient to thicken the composition. In certain aspects, the composition cannot include any exogenous additives that have crystallization-inhibiting properties that are not naturally occurring in oils in amounts sufficient to inhibit crystal formation. In other aspects, the composition cannot include any exogenous additives that have thickening or crystallization-inhibiting properties that are not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively.

[0093] In any of the foregoing embodiments, the EMO, FFA oil and / or oil can be substantially free of 3-monochloropanediol and glycidol equivalents.

[0094] In any of the foregoing embodiments, the composition cannot include a quaternary amine.

[0095] In any of the foregoing embodiments, the composition cannot include a polyhydric alcohol.

[0096] In any of the foregoing embodiments, the composition cannot include bile salts.

[0097] In any of the foregoing embodiments, the droplets may be mixed micelles. Alternatively, in any of the foregoing embodiments, the particles may be solid lipid particles.

[0098] In some embodiments, a method of preparing a nanoemulsion is provided that includes providing an oil of the present disclosure, providing a polar liquid component, combining the oil and the polar liquid component to form a nanoemulsion premix, and forming a nanoemulsion from the nanoemulsion premix, wherein the nanoemulsion includes an oil phase and a polar liquid phase, the oil phase being dispersed as droplets or particles within the polar liquid phase, the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering. In certain embodiments, the oil can be heated, e.g., to 60° C., prior to combining with the polar liquid component, and the polar liquid component itself can be preheated, e.g., to 60° C. As a further example, but not limited to, the oil can be heated to about 40° C. to about 80° C., about 40° C. to about 70° C., about about 50° C. to about 80° C., about 50° C. to about 70° C., about 55° C. to about 65° C., about 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C., or 80° C. As a still further example, but not limited to, the polar liquid can be preheated to about 40° C. to about 80° C., about 40° C. to about 70° C., about about 50° C. to about 80° C., about 50° C. to about 70° C., about 55° C. to about 65° C., about 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C., or 80° C.

[0099] In any of the foregoing method embodiments, the nanoemulsion can be formed under conditions sufficient to have the properties of any of the compositions of the foregoing embodiments.

[0100] In any of the embodiments of the method described above, the method can further include blending one or more oil components to form an oil. In some embodiments, the one or more oil components are derived from different oil sources or combinations thereof, as described in this disclosure. In some embodiments, the one or more oil components are derived from the same oil source. By way of example and not limitation, the one or more oil components can be selected from EMO, FFA oil, unmodified TAG oil, and combinations thereof.

[0101] It is to be understood that the polar liquid medium can be any suitable polar liquid medium, including those disclosed in this disclosure with respect to the compositions of the present disclosure.

[0102] By way of example and not limitation, a nanoemulsion can be formed by rapid addition of a polar liquid phase to an oil phase, or by mixing to form a coarse emulsion and then homogenizing by sonicating the coarse emulsion to form the nanoemulsion. By way of further example and not limitation, a nanoemulsion can be formed by dropwise addition of oil to a polar liquid phase to form a coarse emulsion and then sonicating the coarse emulsion to form the nanoemulsion.

[0103] It is understood that other methods for making nanoemulsions are well known and can be used by those of skill in the art to prepare the nanoemulsions of the present disclosure, including, but not limited to, high shear homogenization, microfluidization, bath sonication, solvent evaporation, supercritical fluid techniques, spray drying, and double emulsion techniques.

[0104] Microemulsions and large nanoemulsions It is also understood that although the compositions of the present disclosure are disclosed as nanoemulsions, they can also be formulated as larger nanoemulsions or microemulsions depending on the application. In any of the above embodiments, rather than the droplets or particles having a Z-average size of about 300 nm or less, the droplets or particles can have a Z-average size of greater than about 300 nm or greater than about 1000 nm. By way of example, and not limitation, in addition to the sizes of nanoemulsion compositions already disclosed, the droplets or particles may be greater than about 300 nm, greater than about 400 nm, greater than about 500 nm, greater than about 600 nm, greater than about 700 nm, greater than about 800 nm, greater than about 900 nm, greater than about 1000 nm, greater than about 10,000 nm, greater than about 100,000 nm, from about 300 nm to about 1000 nm, from about 500 nm to about 1000 nm, from about 750 to about 1000 nm, from about 1000 nm to about 999,999 nm, from about 1000 nm to about 100,000 nm, from about The nanoemulsion may have a Z-average size of about 10,000 nm to about 10,000 nm, about 10,000 to about 5,000 nm, about 1000 to about 3,000 nm, about 300 nm, about 400 nm, about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm, about 1000 nm, about 2,000 nm, about 3,000 nm, about 4,000 nm, about 5,000 nm, about 10,000 nm, about 20,000 nm, about 30,000 nm, about 40,000 nm, about 50,000 nm, about 100,000 nm, or about 1,000,000 nm. As a further example, but not limited to, microemulsions may be used instead of nanoemulsions for certain active ingredient delivery applications. By way of example, but not limited to, the size of microemulsions and larger nanoemulsions may be measured by microscopy or dynamic light scattering.

[0105] Methods for producing microemulsions and larger nanoemulsions are well known in the art, including, but not limited to, homogenization, sonication, solvent evaporation, supercritical fluids, spray drying, and double emulsion. As a further example, but not limited to, the process of forming a coarse nanoemulsion by homogenization disclosed in the present application can be used to form microemulsions and larger nanoemulsions. In the disclosed method for forming a nanoemulsion, the method can be modified to form a microemulsion by using a conventional method for forming a microemulsion instead of forming a nanoemulsion. It should be understood that a similar method can be used to obtain a larger nanoemulsion, if necessary. It should also be understood that the method for preparing a nanoemulsion of the present disclosure can be used to the extent that it produces a larger nanoemulsion or microemulsion. As an example, but not limited to, to form a larger nanoemulsion or microemulsion, the oil can be optionally heated first and then mixed with a polar liquid and subjected to homogenization. As a further example, and not by way of limitation, the polar liquid can be preheated prior to combining with the oil.

[0106] Non-nanoemulsion Compositions It should be understood that in the compositions comprising the nanoemulsions and microemulsions of the present disclosure, the oil can be either EMO, FFA oil, or a combination of both. It should be further understood that the compositions of the present disclosure encompass any of the above-mentioned embodiments in which the composition has any of the recited properties, but does not have droplets or particles, and is an oil composition. Thus, the only property that differs in such embodiments is that the composition is not a nanoemulsion or microemulsion, and does not have the recited size, zeta potential, PDI, or stability properties. Similarly, it should be understood that in such embodiments, the composition may include an oil, but does not necessarily need to be a liquid, as disclosed in certain nanoemulsion embodiments.

[0107] In some embodiments, an oil composition is provided that includes an oil of about 10% to about 80% by weight monoacylglycerol (MAG) and an oil of free fatty acids in an amount of 5% to about 75% by weight, wherein the combination of MAG and free fatty acids is about 60% to about 95% by weight of the total weight of the oil, the free fatty acids include two or more different fatty acids, and the oil is substantially free of triacylglycerol (TAG).By way of example and not limitation, the oil composition may comprise from about 10% to about 80% by weight, from about 15% to about 80% by weight, from about 20% to about 80% by weight, from about 25% to about 80% by weight, from about 30% to about 80% by weight, from about 40% to about 80% by weight, from about 50% to about 80% by weight, from about 60% to about 80% by weight, from about 70% to about 80% by weight, from about 75% to about 80% by weight, from about 10% to about 75% by weight, from about 15% to about 75% by weight, from about 20% to about 75% by weight, from about 25% to about 75% by weight , about 30% to about 75% by weight, about 40% to about 75% by weight, about 50% to about 75% by weight, about 60% to about 75% by weight, about 70% to about 75% by weight, about 10% to about 70% by weight, about 15% to about 70% by weight, about 20% to about 70% by weight %25% to 70%, 30% to 70%, 40% to 70%, 50% to 70%, 60% to 70%, 10% to 60%, 15% to 60%, 20% to 60% %, about 25% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50% Amount%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 15% to about 40%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 10% to about 30 %, about 15% by weight to about 30% by weight, about 20% by weight to about 30% by weight, about 25% by weight to about 30% by weight, about 10% by weight to about 25% by weight, about 15% by weight to about 25% by weight, about 20% by weight to about 25% by weight, about 10% by weight to about 20% by weight, about 15% by weight to about 20% by weight, about 10% by weight to about 15% by weight, or about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, or 80% by weight of MAG.By way of example, and without limitation, the free fatty acids may comprise from about 5% to about 75% by weight, about 10% to about 75% by weight, about 15% to about 75% by weight, about 20% to about 75% by weight, about 25% to about 75% by weight, about 30% to about 75% by weight, about 40% to about 75% by weight, about 50% to about 75% by weight, about 60% to about 75% by weight, about 70% to about 75% by weight, about 10% to about 70% by weight, about 15% to about 75% by weight, about 20 ...40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to about 75% by weight, about 40% to 5% by weight, about 40% to about 75% by weight, about 50% to about 75% by weight, about 60% to about 75% by weight, about 70% to about 75% by weight, about 10% to about 70% by weight, about 15% to about 70% by weight, about 20% to about 70% by weight, about 25% by weight About 70% by weight, about 30% to about 70% by weight, about 40% to about 70% by weight, about 50% to about 70% by weight, about 60% to about 70% by weight, about 10% to about 60% by weight, about 15% to about 60% by weight, about 20% to about 60% by weight, about 25% by weight Amount%~60% by weight, about 30%~60% by weight, 40%~60%, 50%~60%, 10%~50%, 15%~50%, 20%~50%, 25%~50%, approx. 30% to about 50% by weight, about 40% to about 50% by weight, about 10% to about 40% by weight, about 15% to about 40% by weight, about 20% to about 40% by weight, about 25% to about 40% by weight, about 30% to about 40% by weight, about 10% to about 30% by weight %, about 15% by weight, to about 30% by weight, about 20% by weight, to about 30% by weight, about 25% by weight, to about 30% by weight, about 10% by weight, to about 25% by weight, about 15% by weight, to about 25% by weight, about 20% by weight, to about 25% by weight, about 10% by weight, to about 20% by weight, about 15% by weight, to about 20% by weight, about 10% by weight, to about 15% by weight, or about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, or 75% by weight of the FFA.By way of example, and without limitation, the combined amount of MAG and FFA may be about 60% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, about 90% to about 95% by weight, about 60% to about 90% by weight, about 70% to about 90% by weight, about 75% to about 90% by weight, about 80% to about 90% by weight, about 60% to about 80% by weight, about 70% to about 80% by weight, about 75% to about 80% by weight, about 60% to about 75% by weight, about 70% to about 75% by weight, about 60% to about 70% by weight, or about 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% by weight of the total weight of the oil.

[0108] In any of the foregoing embodiments, the oil composition may be a mixture of EMO and FFA oils. In other embodiments, the oil composition is an EMO. In yet other embodiments, the oil composition is an FFA oil.

[0109] In any of the foregoing embodiments, the oil may have a fatty acid profile that includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 of C6:0, C8:0, C10, C12, C14, C16, C18, C18:1, C18:2, C18:3, C20, and C22, each fatty acid ranging from about 0.1% to 85% of the total fatty acid content. By way of example and not limitation, for each fatty acid, the amount may be from about 0.1% to about 85%, from about 0.5% to about 85%, from about 1% to about 85%, from about 2% to about 85%, from about 3% to about 85%, from about 4% to about 85%, from about 5% to about 85%, from about 10% to about 85%, from about 15% to about 85%, from about 20% to about 85%, from about 25% to about 85%, from about 30% to about 85%, from about 35% to about 85%, from about 40 ... About 85%, about 45% to about 85%, about 50% to about 85%, about 55% to about 85%, about 60% to about 85%, about 65% to about 85%, about 70% to about 85%, about 75% to about 85%, about 80% to about 85%, about 0.1% to about 80%, about 0.5% to about 80%, about 1% to about 80%, about 2% to about 80%, about 3% to about 80%, about 4% to about 80%, about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, about 65% to about 80%, about 70% to about 80%, about 75% to about 80%, about 0.1% to about 75%, about 0.5% to about 75%, about 1% to about 75%, about 2% to about 75%, about 3% ~ about 75%, about 4% to about 75%, about 5% to about 75%, about 10% to about 75%, about 15% to about 75%, about 20% to about 75%, about 25% to about 75%, about 30% to about 75%, about 35% to about 75%, about 40% to about 75%, about 45% to about 75%, about 50% to about 75%, about 55% to about 75%, about 60% to about 75%, about 65% to about 75%, about 70% to about 75%, about 0.1% to about 70%, about 0.5% to about 70%, about 1% to about 70%, about 2% to about 70%, about 3% to about 70%, about 4% to about 70%, about 5% to about 70%, about 10% to about 70%, about 15% to about 70%, about 20% to about 70%, about 25% to about 70%, about 30% to about 70%, about 35% to about 70%, about 40% to about 70%, about 45% to about 70%, about 50% to about 70%, about 55% to about 70%, about 60% to about 70%, about 65% to about 70%, about 0.1% to about 65%, about 0.5% to about 65%, about 1% to about 65%, about 2% to about 65%, about 3% to about 65%, about 4% to about 65%, about 5% to about 65%, about 10 % to about 65%, about 15% to about 65%, about 20% to about 65%, about 25% to about 65%, about 30% to about 65%, about 35% to about 65%, about 40% to about 65%, about 45% to about 65%, about 50% to about 65%, about 55% to about 65%, about 60% to about 65%, about 0.1% to about 60%, about 0.5% to about 60%, about 1% to about 60%, about 2% to about 60%, about 3% to about 60%, about 4% to about 60%, about 5% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 40% to about 60% , about 45% to about 60%, about 50% to about 60%, about 55% to about 60%, about 0.1% to about 55%, about 0.5% to about 55%, about 1% to about 55%, about 2% to about 55%, about 3% to about 55%, about 4% to about 55%, about 5% to about 55%, about 10% to about 55%, about 15% to about 55%, about 20% to about 55%, about 25% to about 55%, about 30% to about 55%, about 35% to about 55%, about 40% to about 55%, about 45% to about 55%, about 50% to about 55%, about 0.1% to about 50%, about 0.5% to about 50%, about 1% to about 50%, about 2% to about 50%, about 3% to about 50%, about 4% to about 5 0%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50%, about 45% to about 50%, about 0.1% to about 45%, about 0.5% to about 45%, about 1% to about 45%, about 2% to about 45%, about 3% to about 45%, about 4% to about 45%, about 5% to about 45%, about 10% to about 45%, about 15% to about 45%, about 20% to about 45%, about 25% to about 45%, about 30% to about 45%, about 35% to about 45%, about 40% to about 45%, about 0.1% to about 40%, about 0.5% to about 40%, about 1% to about 40%, about 2% to about 40%, about 3% to about 40%, about 4% to about 40%, about 5% to about 40%, about 10% to about 40%, about 15% to about 40%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 35% to about 40%, about 0.1% to about 35% , about 0.5% to about 35%, about 1% to about 35%, about 2% to about 35%, about 3% to about 35%, about 4% to about 35%, about 5% to about 35%, about 10% to about 35%, about 15% to about 35%, about 20% to about 35%, about 25% to about 35%, about 30% to about 35%, about 0.1% to about 30%, about 0.5% to About 30%, about 1% to about 30%, about 2% to about 30%, about 3% to about 30%, about 4% to about 30%, about 5% to about 30%, about 10% to about 30%, about 15% to about 30%, about 20% to about 30%, about 25% to about 30%, about 0.1% to about 25%, about 0.5% to about 25%, about 1% to about 25%, about 2 % to about 25%, about 3% to about 25%, about 4% to about 25%, about 5% to about 25%, about 10% to about 25%, about 15% to about 25%, about 20% to about 25%, about 0.1% to about 20%, about 0.5% to about 20%, about 1% to about 20%, about 2% to about 20%, about 3% to about 20%, about 4% to about 20%, about 5 % to about 20%, about 10% to about 20%, about 15% to about 20%, about 0.1% to about 15%, about 0.5% to about 15%, about 1% to about 15%, about 2% to about 15%, about 3% to about 15%, about 4% to about 15%, about 5% to about 15%, about 10% to about 15%, about 0.1% to about 10%, about 0.5% to about 1 0%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 0.1% to about 5%, about 0.5% to about 5%, about 1% to about 5%, about 2% to about 5%, about 3% to about 5%, about 4% to about 5%, about 0.1% to about 4%, about 0.5% to about 4%, about 1% to It may be about 4%, about 2% to about 4%, about 3% to about 4%, about 0.1% to about 3%, about 0.5% to about 3%, about 1% to about 3%, about 2% to about 3%, about 0.1% to about 2%, about 0.5% to about 2%, about 1% to about 2%, about 0.1% to about 1%, about 0.5% to about 1%, or about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% or 85%.

[0110] As an example, and not by way of limitation, when the oil is derived from linseed oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 10% to about 20%, C18:2 in an amount of about 10% to about 20%, and C18:3 in an amount of about 50% to about 65%.

[0111] As an example, and not by way of limitation, when the oil is derived from MCT oil, the two or more different fatty acids can include two or more fatty acids derived from C8:0 in an amount of about 50% to about 65% of the total fatty acid content of the oil, and C10 in an amount of about 35% to about 50% of the total fatty acid content of the oil.

[0112] By way of example, and not limitation, when the oil is derived from rosehip oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 15% to about 25% of the total fatty acid content of the oil, C18:2 in an amount of about 45% to about 55% of the total fatty acid content of the oil, and C18:3 in an amount of about 15% to about 25% of the total fatty acid content of the oil.

[0113] As an example, and not by way of limitation, when the oil is derived from sesame oil, the two or more different fatty acids can include two or more fatty acids derived from C18 in an amount of about 10% to about 20% of the total fatty acid content of the oil, C18:1 in an amount of about 35% to about 45% of the total fatty acid content, and C18:2 in an amount of about 30% to about 45% of the total fatty acid content.

[0114] By way of example, and not limitation, when the oil is derived from hemp seed oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 5% to about 20% of the total fatty acid content of the oil, C18:2 in an amount of about 50% to about 65% of the total fatty acid content, and C18:3 in an amount of about 15% to about 25% of the total fatty acid content.

[0115] As an example, and not by way of limitation, when the oil is derived from sunflower oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 15% to about 25% of the total fatty acid content of the oil, and C18:2 in an amount of about 60% to about 80% of the total fatty acid content.

[0116] As an example, and not by way of limitation, when the oil is derived from canola oil, the two or more different fatty acids can include two or more fatty acids derived from C18:1 in an amount of about 55% to about 70% of the total fatty acid content of the oil, and C18:2 in an amount of about 15% to about 30% of the total fatty acid content.

[0117] As an example, and not by way of limitation, when the oil is derived from almond oil, the two or more different fatty acids can include two or more fatty acids: C18:1 in an amount of about 60% to about 80% of the total fatty acid content of the oil, and C18:2 in an amount of about 10% to about 25% of the total fatty acid content of the oil.

[0118] By way of example, and not limitation, when the oil is derived from olive oil, the two or more different fatty acids can include two or more fatty acids derived from C16 in an amount between about 5% and about 20% of the total fatty acid content of the oil, C18:1 in an amount between about 65% and about 80% of the total fatty acid content, and C18:2 in an amount between about 5% and about 15% of the total fatty acid content.

[0119] By way of example, and not limitation, when the oil is derived from oat oil, the two or more different fatty acids can include two or more fatty acids derived from C16 in an amount of about 5% to about 20% of the total fatty acid content of the oil, C18:1 in an amount of about 15% to about 30% of the total fatty acid content, and C18:2 in an amount of about 45% to about 60% of the total fatty acid content.

[0120] In any of the foregoing embodiments, the EMO and / or FFA oil can have a triacylglycerol (TAG) content of 5 wt.% or less TAG, based on the total weight of the EMO and / or FFA oil, respectively. By way of example and without limitation, the TAG content can be 4 wt.% or less, 3 wt.% or less, 2 wt.% or less, 1 wt.% or less, based on the total weight of the EMO, FFA oil, or oil composition, respectively, or the EMO and / or FFA oil can be substantially free of TAG.

[0121] It should be understood that the EMO and / or FFA oils may be derived from the oil sources described herein, including the first oil source and the second oil source, respectively, as provided in the preceding embodiments.

[0122] In any of the above embodiments, the EMO and / or FFA oils can further comprise non-oil components derived from the first oil source or the second oil source, respectively, and naturally occurring. By way of example and without limitation, the non-oil components derived from the oil source, the first oil source or the second oil source, and naturally occurring can include glycosphingolipids such as ceramide phosphate, glycoglycerolipids such as monogalactosyl diacylglycerol, phophatidyl alcohols such as phosphatidylmethanol, steroids such as sitosteryl esters, natural lipids such as campesterol esters, sphingolipids, phosphatidylglycerols, wax esters, sphingomyelins, phosphatides, plant sterols (campesterol, stigmasterol, sitosterol), cholesterol, tocopherols, tocotrienols, carotenes, xanthophylls, betaxanthins, chlorophylls, long chain alcohols, polyphenols, The active ingredient may include terpenes (cycloartanol, cycloarterenol, 24-methylenecycloarterenol), terpenoids (squalene), tocopherols, vitamins, paraffins, isothiocyanates, oxazolidinethiones, glucosinolates, sanguinarine, gossypol, glycosylated alkaloids, phospholipids, sphingosine, diacylglyceride ethers, glycolipids, phytic acid, quinic acid, oxalic acid, tartaric acid, anacardic acid, malic acid, caftaric acid, ctaranic acid, fertharic acid, phenylethanoids, hydroxycinnamic acids, phenolic acids, phytoestrogens, lignans, isoflavonoids, flavonoids, monoterpenes, diterpenes, triterpenoids, coenzymes, or combinations thereof. By way of further example, and without limitation, non-oil components derived and naturally occurring from the first oil source or the second oil source can include ceramide phosphate, monoglactodiacylglycerol, phosphatidylmethanol, sitosteryl esters, campestrol esters, sphingolipids, phosphatidylglycerol, wax esters, sphingomyelin, or combinations thereof.As yet further examples, but not limited to, the non-oil components derived from and naturally occurring in the first or second oil source can include α-tocopherol, β-tocopherol, δ-tocopherol, γ-tocopherol, α-tocotrienol, β-tocotrienol, δ-tocotrienol, γ-tocotrienol, or combinations thereof. In certain embodiments, the non-oil components derived from and naturally occurring in the first or second oil source are present in the EMO or FFA oil in a characteristic or relative amount or increased amount relative to the amount or relative amount of the first or second oil source, respectively. It should be understood that the level of the non-oil components can generally be the same as or exceed the level in the oil source. By way of example, but not limited to, the non-oil components can be determined by LC / MS / MS analysis.

[0123] In any of the foregoing embodiments, the MAG in the EMO (or oil composition) can have a ratio of sn-1 substitution to sn-2 substitution of greater than 1. By way of example and not limitation, the MAG in the EMO (or oil composition) can have a ratio of sn-1 substitution to sn-2 substitution of greater than 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, or 100. By way of example and not limitation, the sn-1 / sn-2 ratio can be determined by TLC or HPLC.

[0124] In any of the foregoing embodiments, the EMO may comprise free fatty acids (FFAs). In any of the foregoing embodiments, the EMO may comprise an FFA content of 5% or more by weight of the total weight of the EMO. By way of example, and not limitation, EMO may be present in an amount of about 5% to about 66% by weight, about 10% to about 66% by weight, about 20% to about 66% by weight, about 30% to about 66% by weight, about 40% to about 66% by weight, about 50% to about 66% by weight, about 5% to about 60% by weight, about 10% to about 60% by weight, about 20% to about 60% by weight, about 30% to about 60% by weight, about 40% to about 60% by weight, about 50% to about 60% by weight, about 5% to about 50% by weight, about 10% to about 50% by weight, about 20% to about 50% by weight, about 30% to about 50% by weight, The FFA content may be about 40% to about 50% by weight, about 5% to about 40% by weight, about 10% to about 40% by weight, about 20% to about 40% by weight, about 30% to about 40% by weight, 5% to about 30% by weight, about 10% to about 30% by weight, about 20% to about 30% by weight, about 5% to about 20% by weight, about 10% to about 20% by weight, about 5% to about 10% by weight, or about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or 66% by weight.

[0125] In any of the foregoing embodiments, the FFA oil can comprise free fatty acids (FFAs). In any of the foregoing embodiments, the FFA oil can comprise an FFA content of 1% or more by weight of the total weight of the FFA oil. By way of example, and without limitation, the FFA oil may be from about 1% to about 95%, from about 5% to about 95%, from about 10% to about 95%, from about 15% to about 95%, from about 20% to about 95%, from about 25% to about 95%, from about 30% to about 95%, from about 40% to about 95%, from about 50% to about 95%, from about 60% to about 95%, from about 70% to about 95%, from about 75% to about 95%, from about 80% to about 95%, from about 90% to about 95%, from about 1% to about 90%, from about 5% to about 90%, from about 10% to about 90%, from about 15% to about 90%, from about 20% to about 90%, from about 25% to about 90%, from about 30% to about 90%, About 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 75% to about 90%, about 80% to about 90%, about 1% to about 80%, about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 75% to about 80%, about 1% to about 75%, about 5% to about 75%, about 10% to about 75%, about 15% to about 75%, about 20% to about 75% , about 25% to about 75%, about 30% to about 75%, about 40% to about 75%, about 50% to about 75%, about 60% to about 75%, about 70% to about 75%, about 1% to about 70%, about 5% to about 70%, about 10% to about 70%, about 15% to about 70%, about 20% to about 70%, about 25% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 1% to about 60%, about 5% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60 %, about 40% to about 60%, about 50% to about 60%, about 1% to about 50%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 40% to about 50%, about 1% to about 40%, about 5% to about 40%, about 10% to about 40%, about 15% to about 40%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 1% to about 30%, about 5% to about 30%, about 10% to about 30%, about 15% to about 30%, about 20% to about 30%, about 25% to about 30%,About 1% to about 25%, about 5% to about 25%, about 10% to about 25%, about 15% to about 25%, about 20% to about 25%, about 1% to about 20%, about 5% to about 20%, about 10% to about 20%, about 15% to about 20%, about 1% to about 15%, about 5% to about 15%, about 10% to about 15%, about 1% to about 10%, about 5% to about 10%, about 1% to about 5%, about 1%, 5%, 10%, 15% , 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, or 95%, or 1%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, or 95% or more FFA content.

[0126] In any of the foregoing embodiments, the EMO (and thus the oil composition, if EMO is present) may include monoacylglycerol (MAG). In any of the foregoing embodiments, the EMO may include a MAG content of 30% or more by weight of the total weight of the EMO. By way of example and not limitation, the EMO may include about 30% to about 95% by weight, about 40% to about 95% by weight, about 50% to about 95% by weight, about 60% to about 95% by weight, about 70% to about 95% by weight, about 80% to about 95% by weight, about 90% to about 95% by weight, about 30% to about 90% by weight, about 40% to about 90% by weight, about 50% to about 90% by weight, about 60% to about 90% by weight, about 80% to about 90% by weight, about 50% to about 90% by weight, about 30% to about 80% by weight, about 40% to about 8 ... The MAG content may be about 80% by weight, about 60% to about 80% by weight, about 70% to about 80% by weight, about 30% to about 70% by weight, about 40% to about 70% by weight, about 50% to about 70% by weight, about 50% to about 60% by weight, about 30% to about 50% by weight, about 40% to about 50% by weight, or about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% by weight.

[0127] In any of the foregoing embodiments, the EMO (and thus the oil composition, if EMO is present) can include diacylglycerol (DAG). In any of the foregoing embodiments, the EMO can include a DAG content of 5% or more by weight of the total weight of the EMO. By way of example, and not limitation, EMO may be present in an amount of about 5% to about 66% by weight, about 10% to about 66% by weight, about 20% to about 66% by weight, about 30% to about 66% by weight, about 40% to about 66% by weight, about 50% to about 66% by weight, about 5% to about 60% by weight, about 10% to about 60% by weight, about 20% to about 60% by weight, about 30% to about 60% by weight, about 40% to about 60% by weight, about 50% to about 60% by weight, about 5% to about 50% by weight, about 10% to about 50% by weight, about 20% to about 50% by weight, about 30% to about 50% by weight, The DAG content may be about 40% to about 50% by weight, about 5% to about 40% by weight, about 10% to about 40% by weight, about 20% to about 40% by weight, about 30% to about 40% by weight, 5% to about 30% by weight, about 10% to about 30% by weight, about 20% to about 30% by weight, about 5% to about 20% by weight, about 10% to about 20% by weight, about 5% to about 10% by weight, or about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or 66% by weight.

[0128] In any of the foregoing embodiments, the EMO can have a fatty acid profile that includes amounts of two or more fatty acids, where the amount of each of the two or more fatty acids is within 10% of the amount of each of the two or more fatty acids in the first oil source. By way of example and not limitation, the EMO can have a fatty acid profile that includes amounts of three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten, eleven, or twelve of C6:0, C8:0, C10, C12, C14, C16, C18, C18:1, C18:2, C18:3, C20, and C22, where the amount of each of the fatty acids is within 10% of, or is about the same amount as, the amounts of each of the fatty acids: 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%. For example, if the first oil source has 15% C18 fatty acids, the EMO can have about 5-25%, 6-24%, 7-23%, 8-22%, 9-21%, 10-20%, 11-19%, 12-18%, 13-17%, 14-16% or about 15% C18 fatty acids.

[0129] It should be understood that in any of the foregoing embodiments, the first oil source and the second oil source may be the same type of oil or different types of oil, and each of the first oil source and the second oil source may be a single type of oil (e.g., oat oil or linseed oil) or a combination of oils, as further described herein. Similarly, it should be further understood that the EMO and / or FFA oil may be the result of a blend of EMO and / or FFA oils, respectively, which have been processed independently and subsequently combined, such that the first oil source or the second oil source, respectively, is a combination of oil sources used to produce different EMO and / or FFA oils that have been combined.

[0130] In any of the above embodiments, the EMO and FFA oils each may contain two or more different fatty acids. In any of the above embodiments, the two or more different fatty acids may be selected from the group consisting of, for example and without limitation, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, heptadecenoic acid, stearic acid, nonadecylic acid, vaccenic acid, oleic acid, linoleic acid, linolenic acid, stearidonic acid, octadecatetraenoic acid, arachidic acid, heneicosyl acid, gondoic acid, eicosadienoic acid, paulic acid, behenic acid, tricosyl acid, erucic acid, lignoceric acid, docosahexaenoic acid, eicosapentenoic acid, nervonic acid, and isomers thereof. Alternatively, the fatty acids comprising the two or more different fatty acids may each independently be selected from the group consisting of C6 fatty acids, such as, for example and not limited to, C6:0, C7 fatty acids, C8 fatty acids, such as, for example and not limited to, C8:0 fatty acids, C9 fatty acids, C10 fatty acids, C11 fatty acids, C12 fatty acids, C13 fatty acids, C14 fatty acids, C15 fatty acids, C16 fatty acids, C17 fatty acids, C18 fatty acids, such as, for example and not limited to, C18:0 fatty acids, C18:0 fatty acids, C18:1 fatty acids, C18:2 fatty acids, or C18:3 fatty acids, C19 fatty acids, C20 fatty acids, such as, for example and not limited to, C20:5 fatty acids, C21 fatty acids, C22 fatty acids, such as, for example and not limited to, C22:6 fatty acids, C23 fatty acids, and C24 fatty acids. It should be understood that the two or more different fatty acids may be the same or different between the EMO and FFA oils.

[0131] In any of the foregoing embodiments, the two or more different fatty acids can be present in the EMO or FFA oil in an amount within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% of the amount of that fatty acid in the fatty acid profile of the first oil source or the second oil source, respectively. In any of the foregoing embodiments, the two or more different fatty acids can be two fatty acids, three fatty acids, four fatty acids, five fatty acids, six fatty acids, seven fatty acids, eight fatty acids, nine fatty acids, ten or more fatty acids. For example, if the first crude oil has 20% C18:1 fatty acids and 20% C12 fatty acids, the EMO, if within 10% of the amount of fatty acids in the fatty acid profile of the first oil source, will have 10-30% C18:1 and 10-30% C12. Thus, when an oil composition is a blend of EMO and FFA oils from different oil sources, the fatty acid profile of the oil composition will vary according to the ratio of EMO:FFA oils, and the expected ranges can be calculated by one of skill in the art. However, when the EMO and FFA are derived from the same crude oil, the fatty acid profile of the oil composition is expected to be similar to that of the crude oil.

[0132] In any of the foregoing embodiments, the EMO and / or FFA oil (and thus the oil composition) can be substantially free of 3-monochloropropanediol and glycidol equivalents.

[0133] When a blend of EMO (first amount) and FFA oil (second amount) is used in any of the foregoing embodiments, the first amount as a percentage of the sum of the first amount and second amount (i.e., the amount of EMO relative to the amount of EMO and FFA oil) may be from about 0.1% to about 99.9%, from about 0.1% to about 99.8%, from about 0.1% to about 99.5%, from about 0.1% to about 99%, from about 0.1% to about 98%, from about 0.1% to about 97%, from about 0.1% to about 96%, from about 0.1% to about 95%, from about 0.1% to about 94%, from about 0.1% to about 93%, from about 0.1% to about 92%, from about 0.1% to about 91%, from about 0.1% to about 92% and from about 0.1% to about 93%. 1% to about 90%, about 0.1% to about 80%, about 0.1% to about 75%, about 0.1% to about 70%, about 0.1% to about 60%, about 0.1% to about 50%, about 0.1% to about 40%, about 0.1% to about 30%, about 0.1% to about 25%, about 0.1% to about 20%, about 0.1% to about 15%, about 0.1% to about 10%, about 0.1% to about 5%, about 0.1% to about 4%, about 0.1% to about 3%, about 0.1% to about 2%, about 0.1% to about 1%, about 0.1% to about 0.5%, about 0.1% to about 0.2%, 0.2% to about 99.9%, about 0.2% to about 99.8%, about 0.2% to about 99.5%, about 0.2% to about 99 %, about 0.2% to about 98%, about 0.2% to about 97%, about 0.2% to about 96%, about 0.2% to about 95%, about 0.2% to about 94%, about 0.2% to about 93%, about 0.2% to about 92%, about 0.2% to about 91%, about 0.2% to about 90%, about 0.2% to about 80%, about 0.2% to about 75%, about 0 0.2% to about 70%, about 0.2% to about 60%, about 0.2% to about 50%, about 0.2% to about 40%, about 0.2% to about 30%, about 0.2% to about 25%, about 0.2% to about 20%, about 0.2% to about 15%, about 0.2% to about 10%, about 0.2% to about 5%, about 0.2% to about 4%, about 0.2% to about 3 %, about 0.2% to about 2%, about 0.2% to about 1%, about 0.2% to about 0.5%, 0.5% to about 99.9%, about 0.5% to about 99.8%, about 0.5% to about 99.5%, about 0.5% to about 99%, about 0.5% to about 98%, about 0.5% to about 97%, about 0.5% to about 96%, about 0.5% to about 95 %, about 0.5% to about 94%, about 0.5% to about 93%, about 0.5% to about 92%, about 0.5% to about 91%, about 0.5% to about 90%, about 0.5% to about 80%, about 0.5% to about 75%, about 0.5% to about 70%, about 0.5% to about 60%, about 0.5% to about 50%, about 0.5% to about 40%, about 0.5% to about 30%, about 0.5% to about 25%, about 0.5% to about 20%, about 0.5% to about 15%, about 0.5% to about 10%, about 0.5% to about 5%, about 0.5% to about 4%, about 0.5% to about 3%, about 0.5% to about 2%, about 0.5% to about 1%, about 1% to about 99.9%, about 1% to about 99.8%, about 1% to about 99.5%, about 1% to about 99%, about 1% to about 98%, about 1% to about 97%, about 1% to about 96%, about 1% to about 95%, about 1% to about 94%, about 1% to about 93%, about 1% to about 92% %, about 1% to about 91%, about 1% to about 90%, about 1% to about 80%, about 1% to about 75%, about 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to about 96%, about 5% to about 95%, about 5% to about 94%, about 5% to about 93%, about 5% to about 92%, about 5% to about 91%, about 5% to about 90%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 60%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 10%, about 10% to about 99.9%, about 10% to about 99.8%, about 10% to about 99.5%, about 10% to about 99%, about 10% to about 98%, about 10% to about 97%, about 10% to about 96%, about 10% to about 95%, about 10% to about 94%, about 10% to about 93%, about 10% to about 92%, about 10% to about 91%, about 10% to about 90%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 25%, about 10% to about 20%, about 20% to about 99.9%, about 20% to about 99.8%, about 20% to about 99.5%, about 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to about 99%, about 30% to about 98%, about 30% to about 97%, about 30% to about 96%, about 30% to about 95%, about 30% to about 94%, about 30% to about 93%, about 30% to about 92%, about 30% to about 91%, about 30% to about 90%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 99.9%, about 40% to about 99.8%, about 40% to about 99.5%, about 40% to about 99%, about 40% to about 98%, about 40% to about 97%, about 40% to about 96%, about 40% to about 95%, about 40% to about 94%, about 40% to about 93%, about 40% to about 92%, about 40% to about 91%, about 40% to about 90%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to about 60%, about 40% to about 50%, about 50% to about 99.9%, about 50% to about 99.8%, about 50% to about 99.5%, about 50% to about 99%, about 50% to about 98%, about 50% to about 97%, about 50% to about 96%, about 50% to About 95%, about 50% to about 94%, about 50% to about 93%, about 50% to about 92%, about 50% to about 91%, about 50% to about 90%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 60%, about 60% to about 99.9%, about 60% to about 99.8%, about 60% to about 99.5%, about 60% to about 99%, about 60% to about 98%, about 60% to about 97%, about 60% to about 96%, about 60% to about 95%, about 60% to about 94%, about 60% to about 93%, about 60% to about 92%, about 60% to about 91%, about 60% to about 90%, about 60 % to about 80%, about 60% to about 75%, about 60% to about 70%, about 70% to about 99.9%, about 70% to about 99.8%, about 70% to about 99.5%, about 70% to about 99%, about 70% to about 98%, about 70% to about 97%, about 70% to about 96%, about 70% to about 95%, about 70% to about 94%, about 70% to about 93%, about 70% to about 92%, about 70% to about 91%, about 70% to about 90%, about 70% to about 80%, about 80% to about 99.9%, about 80% to about 99.8%, about 80% to about 99.5%, about 80% to about 99%, about 80% to about 98%, about 80% to About 97%, about 80% to about 96%, about 80% to about 95%, about 80% to about 94%, about 80% to about 93%, about 80% to about 92%, about 80% to about 91%, about 80% to about 90%, about 90% to about 99.9%, about 90% to about 99.8%, about 90% to about 99.5%, about 90% to about 99%, about 90% to about 98%, about 90% to about 97%, about 90% to about 96%, about 90% to about 95%, about 90% to about 94%, about 90% to about 93%, about 90% to about 92%, about 90% to about 91%, about 91% to about 99.9%, about 91% to about 99.8%, about 91% to about 99.5%, about 91% to about 99%, about 91% to about 98%, about 91% to about 97%, about 91% to about 96%, about 91% to about 95%, about 91% to about 94%, about 91% to about 93%, about 91% to about 92%, about 92% to about 99.9%, about 92% to about 99.8%, about 92% to about 99.5%, about 92% to about 99%, about 92% to about 98%, about 92% to about 97%, about 92% to about 96%, about 92% to about 95%, about 92% to about 94%, about 92% to about 93%, about 93% to about 99.9%, about 93% to about 99.8% , about 93% to about 99.5%, about 93% to about 99%, about 93% to about 98%, about 93% to about 97%, about 93% to about 96%, about 93% to about 95%, about 93% to about 94%, about 94% to about 99.9%, about 94% to about 99.8%, about 94% to about 99.5%, about 94% to about 99%, about 94% to about 98%, about 94% to about 97%, about 94% to about 96%, about 94% to about 95%, about 95% to about 99.9%, about 95% to about 99.8%, about 95% to about 99.5%, about 95% to about 99%, about 95% to about 9 8%, about 95% to about 97%, about 95% to about 96%, about 96% to about 99.9%, about 96% to about 99.8%, about 96% to about 99.5%, about 96% to about 99%, about 96% to about 98%, about 96% to about 97%, about 97% to about 99.9%, about 97% to about 99.8%, about 97% to about 99.5%, about 97% to about 99%, about 97% to about 98%, about 98% to about 99.9%, about 98% to about 99.8%, about 98% to about 99.5%, about 98% to about 99%, about 99% to about 99.9%, about 99% to about 99. The first amount may be about 8%, about 99% to about 99.5%, about 99.5% to about 99.9%, about 99.5% to about 99.8%, about 99.8% to about 99.9%, or about 0.1%, 0.2%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.8%, or 99.9%. As yet a further example, the first amount as a percentage of the sum of the first amount and the second amount may be about 25% to about 75%. Alternatively, the first amount as a percentage of the sum of the first and second amounts can be 0% or 100%, i.e., either pure EMO or pure FFA oil.

[0134] It is understood throughout this disclosure that an EMO, FFA oil, or oil composition, whether nanoemulsion, microemulsion, or otherwise, can contain a fatty acid profile that is within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of two or more different fatty acids, and such fatty acid profiles for a single oil source are provided herein and known to those of skill in the art. In the case of a blend of EMO and FFA oils, the fatty acid profile can be calculated based on the ratio of EMO to FFA oil.

[0135] In any of the above embodiments, including those having nanoemulsions or microemulsions, the following table provides preferred oil sources and ranges. [Table 2] [Table 3]

[0136] Drug delivery methods and compositions In some embodiments, the active composition can comprise any composition comprising a nanoemulsion (or microemulsion or larger nanoemulsion) of any of the preceding embodiments or a non-nanoemulsion composition of the present disclosure and an active ingredient. In any of the preceding embodiments, the active ingredient can be present in the oil of the composition, including the nanoemulsion or microemulsion of droplets or particles. Alternatively, the active ingredient can be present in the aqueous phase of the composition, including the nanoemulsion or microemulsion.

[0137] In some embodiments, the active composition can include a first component, a second component, and a third component, where the first component is selected from the group consisting of a cream, a lotion, an eye drop, an ear drop, a sinus rinse, a spray such as a nasal, oral mucosa, skin or foot treatment, an ointment, a deodorant, a body wash, a shampoo, a scalp treatment, a mouthwash, a toothpaste, a troche, a capsule, a lubricant, a beverage, or a powder, the second component is an additive comprising the composition according to any of the previous embodiments, and the third component is an active ingredient selected from the group consisting of an antibiotic, an antiviral, an antiparasitic, an antifungal, an anticancer drug, a steroid, a nonsteroid, a narcotic analgesic, an immunosuppressant, a central nervous system drug, a cardiovascular drug, a diabetes drug, a nucleic acid, a peptide, a protein, a synthetic chemical molecule, a botanical extract, an antioxidant, and a vitamin or dietary supplement.

[0138] In any of the foregoing embodiments, the active ingredient can be any active ingredient that can be formulated with the nanoemulsion (and microemulsion) and non-nanoemulsion compositions of the present disclosure. By way of example, and without limitation, the active ingredient can be a small molecule drug, a peptide, an antibody, a nucleic acid, or a protein, including a vaccine. By way of example, and without limitation, the active ingredient can be an antibiotic, an antiviral drug, an antiparasitic drug, an antifungal drug, an anticancer drug, a steroid drug, a nonsteroid drug, an opiate analgesic drug, an immunosuppressant drug, a central nervous system drug, a cardiovascular drug, a diabetic drug, a nucleic acid, a peptide, a protein, a synthetic chemical molecule, a botanical extract, an antioxidant, and a vitamin or dietary supplement. By way of further example, and without limitation, the active ingredient can be an antibiotic, an antiviral drug, an antiparasitic drug, an antifungal drug, an anticancer drug, a steroid drug, a nonsteroid drug, an opiate analgesic drug, an immunosuppressant drug, a central nervous system (CNS) drug, a cardiovascular drug, a diabetic drug, or a vitamin or dietary supplement. Non-limiting examples of antibiotics include clarithromycin A, bacitracin, neomycin, polymyxin B, mupirocin, or cyclosporine. Non-limiting examples of antiviral drugs include acyclovir, famciclovir, valacyclovir, famciclovir, penciclovir, cidofovir, or foscarnet. Non-limiting examples of antiparasitic drugs include levamisole, niclosamide, praziquantel, albendazole, diethylcarbamazine, ivermectin, thiabendazole, chloroquine, or hydroxychloroquine. Non-limiting examples of antifungal drugs include amphotericin B, ketoconazole, or ciclopirox. Non-limiting examples of anticancer drugs include 5-fluorouracil, paclitaxel, gemcitabine, 5-aminolevulinic acid, tamoxifen, rapamycin, chloroquine, or hydroxychloroquine. Non-limiting examples of steroid drugs include hydrocortisone, prednisone, prednisolone, clobetasol propionate, triamcinolone, triamcinolone acetonide, testosterone, prasterone, or estradiol.Non-limiting examples of non-steroidal drugs include ibuprofen, crisaborole, diclofenac, aceclofenac, celecoxib, ketoprofen, meloxicam, piroxicam, benvitimod, aspirin, salicylic acid, or naproxen. Non-limiting examples of narcotic analgesics include fentanyl, sufentanil, morphine, codeine, hydromorphone, hydrocodone, oxycodone, oxymorphone, or tramadol. Non-limiting examples of immunosuppressants include tacrolimus, pimecrolimus, cyclosporine, azathioprine, rapamycin, everolimus, or methotrexate. Non-limiting examples of central nervous system drugs include riluzole, ropinirole, caffeine, thiocolchicoside, clozapine, imipramine, doxepin, or nicotine. Non-limiting examples of cardiovascular drugs include olmesartan or barbedilol. A non-limiting example of a diabetes drug is glibenclamide. Non-limiting examples of vitamins or dietary supplements include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, curcumin, cannabidiol (CBD), cannabinoids, tetrahydrocannabinol (THC), avenanthramides, epigallocatechin gallate (EGCG), berberine, inulin, glycyrrhizin, caffeine, capsaicin, or resveratrol. Non-limiting examples of proteins and peptides include thyrotropin-releasing hormone analogs, antigenic peptides, human growth hormone, human immunoglobin G (IgG), insulin, parathyroid hormone, interferon alpha, luteinizing hormone releasing hormone, or duprimumab. As a further example, but not limited to, the active ingredient may be a drug suitable for treating or preventing acne, pain, inflammation, cancer, or a vitamin or an anti-aging compound. As yet further examples, the active ingredient can be lidocaine, bupivacaine, prilocaine, or combinations thereof, aspartyl-alanyl-diketopiperazine (DA-DKP), retinol, retinyl palmitate, trifluoroacetyl tripeptide-2, or hexapeptide-11. In certain embodiments, the active ingredient is lipid soluble. In certain embodiments, the active ingredient is hydrophobic.By way of example and without limitation, the active ingredient may have a logP (octanol-water partition coefficient) value of about 1 to about 6. By way of further example and without limitation, the active ingredient may have a logP value of about 1 to about 6, about 1 to about 5, about 1 to about 4, about 1 to about 3, about 1 to about 2, about 2 to about 6, about 2 to about 5, about 2 to about 4, about 2 to about 3, about 3 to about 6, about 3 to about 5, about 3 to about 4, about 4 to about 6, about 4 to about 5, about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6. By way of yet further example and without limitation, the active ingredient may be cannabidiol (CBD), vitamin E, or carotene. However, it should be understood that the active ingredient may be hydrophilic in certain embodiments. By way of example and without limitation, for transdermal applications, the active ingredient may be hydrophilic. As yet a further example, but not by way of limitation, a hydrophilic active ingredient can have a logP of less than 1, such as about -3 to about 1, about -2 to about 1, about -1 to about 1, about 0 to about 1, about -3, -2.5, -2, -1.5, -1, -0.5, 0, 0.5, or 1. It is understood that the logP can be as measured or predicted. It is understood that if the active ingredient is hydrophilic, it can be present in the aqueous phase of the nanoemulsions or microemulsions of the present disclosure. By way of example, but not by way of limitation, such compositions can be used for transdermal delivery of active ingredients.

[0139] In any of the foregoing embodiments, the active ingredient can be present in the active composition at a concentration of about 0.001 mg / mL to about 10 mg / mL or more. By way of example and not limitation, the active ingredient can be present in a concentration of about 0.001 to about 10 mg / mL, about 0.01 to about 10 mg / mL, about 0.1 to about 10 mg / mL, about 0.5 to about 10 mg / mL, about 1 to about 10 mg / mL, about 2.5 to about 10 mg / mL, about 5 to about 10 mg / mL, about 7.5 to about 10 mg / mL, about 0.001 to about 5 mg / mL, about 0.01 to about 5 mg / mL, or about 0.02 to about 5 mg / mL. The active ingredient may be present in the active composition at a concentration of about 0.1 to about 5 mg / mL, about 0.5 to about 5 mg / mL, about 1 to about 5 mg / mL, about 2 to about 5 mg / mL, about 3 to about 5 mg / mL, about 4 to about 5 mg / mL, about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10 mg / mL or more. By way of further example and without limitation, the active ingredient may be present in the active composition at a value greater than 10 mg / mL, such as about 10, 12.5, 15, 17.5, 20, 25 mg / mL or more. In any of the foregoing embodiments, the active ingredient may be present in the active composition at a therapeutically relevant concentration. A therapeutically relevant concentration may be understood as a concentration sufficient to have a desired therapeutic effect. For example, the desired therapeutic effect can be diagnosing, curing, mitigating, treating or preventing a disease, or affecting a change in a structure or function of a subject's body.

[0140] In any of the foregoing embodiments, for compositions and active compositions of the present disclosure, the active ingredient is at least 0.1 μg / cm for the active ingredient over a period of 4, 5, 6, 7, 8, or 24 hours. 2 By way of example and not limitation, skin permeability can be measured by HPLC across an artificial skin such as a Strat-M membrane. By way of further example and not limitation, the active composition can have a skin permeability of at least 0.1 μg / cm over a 4, 5, 6, 7, 8, or 24 hour period. 2 , at least 0.2 μg / cm 2 , at least 0.3 μg / cm 2, at least 0.4 μg / cm 2 , at least 0.5 μg / cm 2 , at least 0.75 μg / cm 2 , at least 1.0 μg / cm 2 , at least 1.5 μg / cm 2 , at least 2.0 μg / cm 2 , at least 2.5 μg / cm 2 , at least 3.0 μg / cm 2 , at least 3.5 μg / cm 2 , at least 4.0 μg / cm 2 , at least 4.5 μg / cm 2 , at least 5.0 μg / cm 2 , at least 6 μg / cm 2 , at least 7 μg / cm 2 , at least 8 μg / cm 2 , at least 9 μg / cm 2 , at least 10 μg / cm 2 , at least 20 μg / cm 2 , at least 30 μg / cm 2 , at least 40 μg / cm 2 , at least 50 μg / cm 2 , at least 60 μg / cm 2 , at least 70 μg / cm 2 , at least 80 μg / cm 2 , at least 90 μg / cm 2 , at least 100 μg / cm 2 , at least 110 μg / cm 2 , at least 120 μg / cm 2 , at least 130 μg / cm 2 , at least 140 μg / cm 2 , at least 150 μg / cm 2 , at least 160 μg / cm 2 , at least 170 μg / cm 2 , at least 180 μg / cm 2 , at least 190 μg / cm 2 , at least 200 μg / cm 2 , at least 250 μg / cm 2 , at least 300 μg / cm2 , at least 350 μg / cm 2 , at least 400 μg / cm 2 , at least 450 μg / cm 2 , at least 500 μg / cm 2 , at least 1000 μg / cm 2 , about 0.1 to about 2000μg / cm 2 , about 0.1 to about 1500μg / cm 2 , about 0.1 to about 1000μg / cm 2 , about 0.1 to about 500μg / cm 2 , about 0.1 to about 450μg / cm 2 , about 0.1 to about 400μg / cm 2 , about 0.1 to about 350μg / cm 2 , about 0.1 to about 300 μg / cm 2 , about 0.1 to about 250μg / cm 2 , about 0.1 to about 200μg / cm 2 , about 0.1 to about 190μg / cm 2 , about 0.1 to about 180μg / cm 2 , about 0.1 to about 170 μg / cm 2 , about 0.1 to about 160μg / cm 2 , about 0.1 to about 150μg / cm 2 , about 0.1 to about 140μg / cm 2 , about 0.1 to about 130μg / cm 2 , about 0.1 to about 120 μg / cm 2 , about 0.1 to about 110 μg / cm 2 , about 0.1 to about 100μg / cm 2 , about 0.1 to about 90μg / cm 2 , about 0.1 to about 80μg / cm 2 , about 0.1 to about 70μg / cm 2 , about 0.1 to about 60μg / cm 2 , about 0.1 to about 50μg / cm 2 , about 0.1 to about 40μg / cm 2 , about 0.1 to about 30 μg / cm 2 , about 0.1 to about 20μg / cm 2 , about 0.1 to about 10 μg / cm 2 , about 0.1 to about 9μg / cm 2 , about 0.1 to about 8μg / cm2 , about 0.1~about 7μg / cm 2 , about 0.1~about 6μg / cm 2 , about 0.1~about 5μg / cm 2 , about 0.1~about 4.5μg / cm 2 , about 0.1~about 4μg / cm 2 , about 0.1~about 3.5μg / cm 2 , about 0.1~about 3μg / cm 2 , about 0.1~about 2.5μg / cm 2 , about 0.1~about 2μg / cm 2 , about 0.1~about 1.5μg / cm 2 , about 0.1~about 1μg / cm 2 , about 0.1~about 0.75μg / cm 2 , about 0.1~about 0.5μg / cm 2 , about 0.1~about 0.4μg / cm 2 , about 0.1~about 0.3μg / cm 2 , about 0.1~about 0.2μg / cm 2 , about 0.2~about 2000μg / cm 2 , about 0.2~about 1500μg / cm 2 , about 0.2~about 1000μg / cm 2 , about 0.2~about 500μg / cm 2 , about 0.2~about 450μg / cm 2 , about 0.2~about 400μg / cm 2 , about 0.2~about 350μg / cm 2 , about 0.2~about 300μg / cm 2 , about 0.2~about 250μg / cm 2 , about 0.2~about 200μg / cm 2 , about 0.2~about 190μg / cm 2 , about 0.2~about 180μg / cm 2 , about 0.2~about 170μg / cm 2 , about 0.2~about 160μg / cm 2 , about 0.2~about 150μg / cm 2 , about 0.2~about 140μg / cm 2 , about 0.2~about 130μg / cm 2 , about 0.2~about 120μg / cm 2 , about 0.2~about 110μg / cm 2 , about 0.2~about 100μg / cm2 , about 0.2~about 90μg / cm 2 , about 0.2~about 80μg / cm 2 , about 0.2~about 70μg / cm 2 , about 0.2~about 60μg / cm 2 , about 0.2~about 50μg / cm 2 , about 0.2~about 40μg / cm 2 , about 0.2~about 30μg / cm 2 , about 0.2~about 20μg / cm 2 , about 0.2~about 10μg / cm 2 , about 0.2~about 9μg / cm 2 , about 0.2~about 8μg / cm 2 , about 0.2~about 7μg / cm 2 , about 0.2~about 6μg / cm 2 , about 0.2~about 5μg / cm 2 , about 0.2~about 4.5μg / cm 2 , about 0.2~about 4μg / cm 2 , about 0.2~about 3.5μg / cm 2 , about 0.2~about 3μg / cm 2 , about 0.2~about 2.5μg / cm 2 , about 0.2~about 2μg / cm 2 , about 0.2~about 1.5μg / cm 2 , about 0.2~about 1μg / cm 2 , about 0.2~about 0.75μg / cm 2 , about 0.2~about 0.5μg / cm 2 , about 0.2~about 0.4μg / cm 2 , about 0.2~about 0.3μg / cm 2 , about 0.3~about 2000μg / cm 2 , about 0.3~about 1500μg / cm 2 , about 0.3~about 1000μg / cm 2 , about 0.3~about 500μg / cm 2 , about 0.3~about 450μg / cm 2 , about 0.3~about 400μg / cm 2 , about 0.3~about 350μg / cm 2 , about 0.3~about 300μg / cm 2 , about 0.3~about 250μg / cm 2 , about 0.3~about 200μg / cm 2, about 0.3~about 190μg / cm 2 , about 0.3~about 180μg / cm 2 , about 0.3~about 170μg / cm 2 , about 0.3~about 160μg / cm 2 , about 0.3~about 150μg / cm 2 , about 0.3~about 140μg / cm 2 , about 0.3~about 130μg / cm 2 , about 0.3~about 120μg / cm 2 , about 0.3~about 110μg / cm 2 , about 0.3~about 100μg / cm 2 , about 0.3~about 90μg / cm 2 , about 0.3~about 80μg / cm 2 , about 0.3~about 70μg / cm 2 , about 0.3~about 60μg / cm 2 , about 0.3~about 50μg / cm 2 , about 0.3~about 40μg / cm 2 , about 0.3~about 30μg / cm 2 , about 0.3~about 20μg / cm 2 , about 0.3~about 10μg / cm 2 , about 0.3~about 9μg / cm 2 , about 0.3~about 8μg / cm 2 , about 0.3~about 7μg / cm 2 , about 0.3~about 6μg / cm 2 , about 0.3~about 5μg / cm 2 , about 0.3~about 4.5μg / cm 2 , about 0.3~about 4μg / cm 2 , about 0.3~about 3.5μg / cm 2 , about 0.3~about 3μg / cm 2 , about 0.3~about 2.5μg / cm 2 , about 0.3~about 2μg / cm 2 , about 0.3~about 1.5μg / cm 2 , about 0.3~about 1μg / cm 2 , about 0.3~about 0.75μg / cm 2 , about 0.3~about 0.5μg / cm 2 , about 0.3~about 0.4μg / cm 2 , about 0.4~about 2000μg / cm 2 , about 0.4~about 1500μg / cm2 , about 0.4~about 1000μg / cm 2 , about 0.4~about 500μg / cm 2 , about 0.4~about 450μg / cm 2 , about 0.4~about 400μg / cm 2 , about 0.4~about 350μg / cm 2 , about 0.4~about 300μg / cm 2 , about 0.4~about 250μg / cm 2 , about 0.4~about 200μg / cm 2 , about 0.4~about 190μg / cm 2 , about 0.4~about 180μg / cm 2 , about 0.4~about 170μg / cm 2 , about 0.4~about 160μg / cm 2 , about 0.4~about 150μg / cm 2 , about 0.4~about 140μg / cm 2 , about 0.4~about 130μg / cm 2 , about 0.4~about 120μg / cm 2 , about 0.4~about 110μg / cm 2 , about 0.4~about 100μg / cm 2 , about 0.4~about 90μg / cm 2 , about 0.4~about 80μg / cm 2 , about 0.4~about 70μg / cm 2 , about 0.4~about 60μg / cm 2 , about 0.4~about 50μg / cm 2 , about 0.4~about 40μg / cm 2 , about 0.4~about 30μg / cm 2 , about 0.4~about 20μg / cm 2 , about 0.4~about 10μg / cm 2 , about 0.4~about 9μg / cm 2 , about 0.4~about 8μg / cm 2 , about 0.4~about 7μg / cm 2 , about 0.4~about 6μg / cm 2 , about 0.4~about 5μg / cm 2 , about 0.4~about 4.5μg / cm 2 , about 0.4~about 4μg / cm 2 , about 0.4~about 3.5μg / cm 2 , about 0.4~about 3μg / cm 2, about 0.4~about 2.5μg / cm 2 , about 0.4~about 2μg / cm 2 , about 0.4~about 1.5μg / cm 2 , about 0.4~about 1μg / cm 2 , about 0.4~about 0.75μg / cm 2 , about 0.4~about 0.5μg / cm 2 , about 0.5~about 2000μg / cm 2 , about 0.5~about 1500μg / cm 2 , about 0.5~about 1000μg / cm 2 , about 0.5~about 500μg / cm 2 , about 0.5~about 450μg / cm 2 , about 0.5~about 400μg / cm 2 , about 0.5~about 350μg / cm 2 , about 0.5~about 300μg / cm 2 , about 0.5~about 250μg / cm 2 , about 0.5~about 200μg / cm 2 , about 0.5~about 190μg / cm 2 , about 0.5~about 180μg / cm 2 , about 0.5~about 170μg / cm 2 , about 0.5~about 160μg / cm 2 , about 0.5~about 150μg / cm 2 , about 0.5~about 140μg / cm 2 , about 0.5~about 130μg / cm 2 , about 0.5~about 120μg / cm 2 , about 0.5~about 110μg / cm 2 , about 0.5~about 100μg / cm 2 , about 0.5~about 90μg / cm 2 , about 0.5~about 80μg / cm 2 , about 0.5~about 70μg / cm 2 , about 0.5~about 60μg / cm 2 , about 0.5~about 50μg / cm 2 , about 0.5~about 40μg / cm 2 , about 0.5~about 30μg / cm 2 , about 0.5~about 20μg / cm 2 , about 0.5~about 10μg / cm 2, about 0.5~about 9μg / cm 2 , about 0.5~about 8μg / cm 2 , about 0.5~about 7μg / cm 2 , about 0.5~about 6μg / cm 2 , about 0.5~about 5μg / cm 2 , about 0.5~about 4.5μg / cm 2 , about 0.5~about 4μg / cm 2 , about 0.5~about 3.5μg / cm 2 , about 0.5~about 3μg / cm 2 , about 0.5~about 2.5μg / cm 2 , about 0.5~about 2μg / cm 2 , about 0.5~about 1.5μg / cm 2 , about 0.5~about 1μg / cm 2 , about 0.5~about 0.75μg / cm 2 , about 1~about 2000μg / cm 2 , about 1 ~ about 1500μg / cm 2 , about 1 to about 1000 μg / cm 2 , about 1 ~ about 500μg / cm 2 , about 1 ~ about 450 μg / cm 2 , about 1 ~ about 400μg / cm 2 , about 1 to about 350 μg / cm 2 , about 1 to about 300 μg / cm 2 , about 1 to about 250 μg / cm 2 , about 1 to about 200 μg / cm 2 , about 1 to about 190 μg / cm 2 , about 1 to about 180 μg / cm 2 , about 1 to about 170 μg / cm 2 , about 1 to about 160 μg / cm 2 , about 1 to about 150 μg / cm 2 , about 1 to about 140 μg / cm 2 , about 1 to about 130 μg / cm 2 , about 1 to about 120 μg / cm 2 , about 1 to about 110 μg / cm 2 , about 1 to about 100 μg / cm 2 , about 1 to about 90 μg / cm 2 , about 1 to about 80 μg / cm 2 , about 1 to about 70 μg / cm 2 , about 1 to about 60 μg / cm 2, about 1 to about 50 μg / cm 2 , about 1 to about 40 μg / cm 2 , about 1 to about 30 μg / cm 2 , about 1 to about 20 μg / cm 2 , about 1 to about 10 μg / cm 2 , about 1 to about 9 μg / cm 2 , about 1 to about 8 μg / cm 2 , about 1 to about 7 μg / cm 2 , about 1 to about 6 μg / cm 2 , about 1 to about 5 μg / cm 2 , about 1 to about 4.5 μg / cm 2 , about 1 to about 4 μg / cm 2 , about 1 to about 3.5 μg / cm 2 , about 1 to about 3 μg / cm 2 , about 1 to about 2.5 μg / cm 2 , about 1~2μg / cm 2 , about 1 to about 1.5 μg / cm 2 , about 2 to about 2000 μg / cm 2 , about 2 to about 1500 μg / cm 2 , about 2 to about 1000 μg / cm 2 , about 2 to about 500 μg / cm 2 , about 2 to about 450 μg / cm 2 , about 2 to about 400 μg / cm 2 , about 2 to about 350 μg / cm 2 , about 2 to about 300 μg / cm 2 , about 2 to about 250 μg / cm 2 , about 2 to about 200 μg / cm 2 , about 2 to about 190 μg / cm 2 , about 2 to about 180 μg / cm 2 , about 2 to about 170 μg / cm 2 , about 2 to about 160 μg / cm 2 , about 2 to about 150 μg / cm 2 , about 2 to about 140 μg / cm 2 , about 2 to about 130 μg / cm 2 , about 2 to about 120 μg / cm 2 , about 2 to about 110 μg / cm 2 , about 2 to about 100 μg / cm 2 , about 2 to about 90 μg / cm 2 , about 2 to about 80 μg / cm 2, about 2 to about 70 μg / cm 2 , about 2 to about 60 μg / cm 2 , about 2 to about 50 μg / cm 2 , about 2 to about 40 μg / cm 2 , about 2 to about 30 μg / cm 2 , about 2 to about 20 μg / cm 2 , about 2 to about 10 μg / cm 2 , about 2 to about 9 μg / cm 2 , about 2 to about 8 μg / cm 2 , about 2 to about 7 μg / cm 2 , about 2 to about 6 μg / cm 2 , about 2 to about 5 μg / cm 2 , about 2 to about 4.5 μg / cm 2 , about 2 to about 4 μg / cm 2 , about 2 to about 3.5 μg / cm 2 , about 2~3μg / cm 2 , about 2 to about 2.5 μg / cm 2 , about 3~about 2000μg / cm 2 , about 3 to about 1500 μg / cm 2 , about 3 to about 1000 μg / cm 2 , about 3 to about 500 μg / cm 2 , about 3 to about 450 μg / cm 2 , about 3 to about 400 μg / cm 2 , about 3 to about 350 μg / cm 2 , about 3 to about 300 μg / cm 2 , about 3 to about 250 μg / cm 2 , about 3 to about 200 μg / cm 2 , about 3 to about 190 μg / cm 2 , about 3 to about 180 μg / cm 2 , about 3 to about 170 μg / cm 2 , about 3 to about 160 μg / cm 2 , about 3 to about 150 μg / cm 2 , about 3 to about 140 μg / cm 2 , about 3 to about 130 μg / cm 2 , about 3 to about 120 μg / cm 2 , about 3 to about 110 μg / cm 2 , about 3 to about 100 μg / cm 2 , about 3 to about 90 μg / cm 2 , about 3 to about 80 μg / cm 2, about 3 to about 70 μg / cm 2 , about 3 to about 60 μg / cm 2 , about 3 to about 50 μg / cm 2 , about 3 to about 40 μg / cm 2 , about 3 to about 30 μg / cm 2 , about 3 to about 20 μg / cm 2 , about 3 to about 10 μg / cm 2 , about 3 to about 9 μg / cm 2 , about 3 to about 8 μg / cm 2 , about 3 to about 7 μg / cm 2 , about 3 to about 6 μg / cm 2 , about 3 to about 5 μg / cm 2 , about 3 to about 4.5 μg / cm 2 , about 3~4μg / cm 2 , about 3~3.5μg / cm 2 , about 4 to about 2000 μg / cm 2 , about 4 to about 1500 μg / cm 2 , about 4 to about 1000 μg / cm 2 , about 4 to about 500 μg / cm 2 , about 4 to about 450 μg / cm 2 , about 4 to about 400 μg / cm 2 , about 4 to about 350 μg / cm 2 , about 4 to about 300 μg / cm 2 , about 4 to about 250 μg / cm 2 , about 4 to about 200 μg / cm 2 , about 4 to about 190 μg / cm 2 , about 4 to about 180 μg / cm 2 , about 4 to about 170 μg / cm 2 , about 4 to about 160 μg / cm 2 , about 4 to about 150 μg / cm 2 , about 4 to about 140 μg / cm 2 , about 4 to about 130 μg / cm 2 , about 4 to about 120 μg / cm 2 , about 4 to about 110 μg / cm 2 , about 4 to about 100 μg / cm 2 , about 4 to about 90 μg / cm 2 , about 4 to about 80 μg / cm 2 , about 4 to about 70 μg / cm 2 , about 4 to about 60 μg / cm 2, about 4 to about 50 μg / cm 2 , about 4 to about 40 μg / cm 2 , about 4 to about 30 μg / cm 2 , about 4 to about 20 μg / cm 2 , about 4 to about 10 μg / cm 2 , about 4 to about 9 μg / cm 2 , about 4 to about 8 μg / cm 2 , about 4 to about 7 μg / cm 2 , about 4 to about 6 μg / cm 2 , about 4 to about 5 μg / cm 2 , about 4 to about 4.5 μg / cm 2 , about 5~about 2000μg / cm 2 , about 5~about 1500μg / cm 2 , about 5 to about 1000 μg / cm 2 , about 5~about 500μg / cm 2 , about 5 to about 450 μg / cm 2 , about 5 to about 400 μg / cm 2 , about 5 to about 350 μg / cm 2 , about 5 to about 300 μg / cm 2 , about 5 to about 250 μg / cm 2 , about 5 to about 200 μg / cm 2 , about 5 to about 190 μg / cm 2 , about 5 to about 180 μg / cm 2 , about 5 to about 170 μg / cm 2 , about 5 to about 160 μg / cm 2 , about 5 to about 150 μg / cm 2 , about 5 to about 140 μg / cm 2 , about 5 to about 130 μg / cm 2 , about 5 to about 120 μg / cm 2 , about 5 to about 110 μg / cm 2 , about 5 to about 100 μg / cm 2 , about 5 to about 90 μg / cm 2 , about 5 to about 80 μg / cm 2 , about 5 to about 70 μg / cm 2 , about 5 to about 60 μg / cm 2 , about 5 to about 50 μg / cm 2 , about 5 to about 40 μg / cm 2 , about 5 to about 30 μg / cm 2 , about 5 to about 20 μg / cm 2, about 5 to about 10 μg / cm 2 , about 5 to about 9 μg / cm 2 , about 5~8μg / cm 2 , about 5~7μg / cm 2 , about 5~6μg / cm 2 , about 6 to about 2000 μg / cm 2 , about 6 to about 1500 μg / cm 2 , about 6 to about 1000 μg / cm 2 , about 6 to about 500 μg / cm 2 , about 6 to about 450 μg / cm 2 , about 6 to about 400 μg / cm 2 , about 6 to about 350 μg / cm 2 , about 6 to about 300 μg / cm 2 , about 6 to about 250 μg / cm 2 , about 6 to about 200 μg / cm 2 , about 6 to about 190 μg / cm 2 , about 6 to about 180 μg / cm 2 , about 6 to about 170 μg / cm 2 , about 6 to about 160 μg / cm 2 , about 6 to about 150 μg / cm 2 , about 6 to about 140 μg / cm 2 , about 6 to about 130 μg / cm 2 , about 6 to about 120 μg / cm 2 , about 6 to about 110 μg / cm 2 , about 6 to about 100 μg / cm 2 , about 6 to about 90 μg / cm 2 , about 6 to about 80 μg / cm 2 , about 6 to about 70 μg / cm 2 , about 6 to about 60 μg / cm 2 , about 6 to about 50 μg / cm 2 , about 6 to about 40 μg / cm 2 , about 6 to about 30 μg / cm 2 , about 6 to about 20 μg / cm 2 , about 6 to about 10 μg / cm 2 , about 6 to about 9 μg / cm 2 , about 6 to about 8 μg / cm 2 , about 6 to about 7 μg / cm 2 , about 7 to about 2000 μg / cm 2 , about 7 to about 1500 μg / cm 2, about 7 to about 1000 μg / cm 2 , about 7 to about 500 μg / cm 2 , about 7 to about 450 μg / cm 2 , about 7 to about 400 μg / cm 2 , about 7 to about 350 μg / cm 2 , about 7 to about 300 μg / cm 2 , about 7 to about 250 μg / cm 2 , about 7 to about 200 μg / cm 2 , about 7 to about 190 μg / cm 2 , about 7 to about 180 μg / cm 2 , about 7~about 1 70 μg / cm 2 , about 7 to about 160 μg / cm 2 , about 7 to about 150 μg / cm 2 , about 7 to about 140 μg / cm 2 , about 7 to about 130 μg / cm 2 , about 7 to about 120 μg / cm 2 , about 7 to about 110 μg / cm 2 , about 7 to about 100 μg / cm 2 , about 7 to about 90 μg / cm 2 , about 7 to about 80 μg / cm 2 , about 7 to about 70 μg / cm 2 , about 7 to about 60 μg / cm 2 , about 7 to about 50 μg / cm 2 , about 7 to about 40 μg / cm 2 , about 7 to about 30 μg / cm 2 , about 7 to about 20 μg / cm 2 , about 7 to about 10 μg / cm 2 , about 7 to about 9 μg / cm 2 , about 7 to about 8 μg / cm 2 , about 8 to about 2000 μg / cm 2 , about 8 to about 1500 μg / cm 2 , about 8 to about 1000 μg / cm 2 , about 8 to about 500 μg / cm 2 , about 8 to about 450 μg / cm 2 , about 8 to about 400 μg / cm 2 , about 8 to about 350 μg / cm 2 , about 8 to about 300 μg / cm 2 , about 8 to about 250 μg / cm2 , about 8 to about 200 μg / cm 2 , about 8 to about 190 μg / cm 2 , about 8 to about 180 μg / cm 2 , about 8 to about 170 μg / cm 2 , about 8 to about 160 μg / cm 2 , about 8 to about 150 μg / cm 2 , about 8 to about 140 μg / cm 2 , about 8 to about 130 μg / cm 2 , about 8 to about 120 μg / cm 2 , about 8 to about 110 μg / cm 2 , about 8 to about 100 μg / cm 2 , about 8 to about 90 μg / cm 2 , about 8 to about 80 μg / cm 2 , about 8 to about 70 μg / cm 2 , about 8 to about 60 μg / cm 2 , about 8 to about 50 μg / cm 2 , about 8 to about 40 μg / cm 2 , about 8 to about 30 μg / cm 2 , about 8 to about 20 μg / cm 2 , about 8 to about 10 μg / cm 2 , about 8 to about 9 μg / cm 2 , about 9 to about 2000 μg / cm 2 , about 9 to about 1500 μg / cm 2 , about 9 to about 1000 μg / cm 2 , about 9 to about 500 μg / cm 2 , about 9 to about 450 μg / cm 2 , about 9 to about 400 μg / cm 2 , about 9 to about 350 μg / cm 2 , about 9 to about 300 μg / cm 2 , about 9 to about 250 μg / cm 2 , about 9 to about 200 μg / cm 2 , about 9 to about 190 μg / cm 2 , about 9 to about 180 μg / cm 2 , about 9 to about 170 μg / cm 2 , about 9 to about 160 μg / cm 2 , about 9 to about 150 μg / cm 2 , about 9 to about 140 μg / cm 2 , about 9 to about 130 μg / cm 2, about 9 to about 120 μg / cm 2 , about 9 to about 110 μg / cm 2 , about 9 to about 100 μg / cm 2 , about 9 to about 90 μg / cm 2 , about 9 to about 80 μg / cm 2 , about 9 to about 70 μg / cm 2 , about 9 to about 60 μg / cm 2 , about 9 to about 50 μg / cm 2 , about 9 to about 40 μg / cm 2 , about 9 to about 30 μg / cm 2 , about 9 to about 20 μg / cm 2 , about 9 to about 10 μg / cm 2 , about 10~about 2000μg / cm 2 , about 10~about 1500μg / cm 2 , about 10~about 1000μg / cm 2 , about 10 ~ about 500μg / cm 2 , about 10~about 450μg / cm 2 , about 10 to about 400 μg / cm 2 , about 10 ~ about 350 μg / cm 2 , about 10 to about 300 μg / cm 2 , about 10~about 250μg / cm 2 , about 10 to about 200 μg / cm 2 , about 10 to about 190 μg / cm 2 , about 10 to about 180 μg / cm 2 , about 10 to about 170 μg / cm 2 , about 10 to about 160 μg / cm 2 , about 10 to about 150 μg / cm 2 , about 10 to about 140 μg / cm 2 , about 10 to about 130 μg / cm 2 , about 10 to about 120 μg / cm 2 , about 10 to about 110 μg / cm 2 , about 10 to about 100 μg / cm 2 , about 10 to about 90 μg / cm 2 , about 10 to about 80 μg / cm 2 , about 10 to about 70 μg / cm 2 , about 10 to about 60 μg / cm 2 , about 10~50μg / cm 2 , about 10~about 40μg / cm 2, about 10 to about 30 μg / cm 2 , about 10~20μg / cm 2 , about 20~about 2000μg / cm 2 , about 20~about 1500μg / cm 2 , about 20~about 1000μg / cm 2 , about 20~500μg / cm 2 , about 20 to about 450 μg / cm 2 , about 20 to about 400 μg / cm 2 , about 20 to about 350 μg / cm 2 , about 20 to about 300 μg / cm 2 , about 20~about 250μg / cm 2 , about 20 to about 200 μg / cm 2 , about 20 to about 190 μg / cm 2 , about 20 to about 180 μg / cm 2 , about 20 to about 170 μg / cm 2 , about 20 to about 160 μg / cm 2 , about 20 to about 150 μg / cm 2 , about 20 to about 140 μg / cm 2 , about 20 to about 130 μg / cm 2 , about 20 to about 120 μg / cm 2 , about 20 to about 110 μg / cm 2 , about 20 to about 100 μg / cm 2 , about 20 to about 90 μg / cm 2 , about 20 to about 80 μg / cm 2 , about 20 to about 70 μg / cm 2 , about 20 to about 60 μg / cm 2 , about 20~50μg / cm 2 , about 20~40μg / cm 2 , about 20~30μg / cm 2 , about 30~about 2000μg / cm 2 , about 30~about 1500μg / cm 2 , about 30~about 1000μg / cm 2 , about 30~500μg / cm 2 , about 30 to about 450 μg / cm 2 , about 30~400μg / cm 2 , about 30~350μg / cm 2 , about 30~300μg / cm 2, about 30~about 250μg / cm 2 , about 30~about 200μg / cm 2 , about 30 to about 190 μg / cm 2 , about 30 to about 180 μg / cm 2 , about 30 to about 170 μg / cm 2 , about 30 to about 160 μg / cm 2 , about 30 to about 150 μg / cm 2 , about 30 to about 140 μg / cm 2 , about 30 to about 130 μg / cm 2 , about 30 to about 120 μg / cm 2 , about 30 to about 110 μg / cm 2 , about 30~100μg / cm 2 , about 30 to about 90 μg / cm 2 , about 30~about 80μg / cm 2 , about 30~70μg / cm 2 , about 30~60μg / cm 2 , about 30~50μg / cm 2 , about 30~40μg / cm 2 , about 40~about 2000μg / cm 2 , about 40~about 1500μg / cm 2 , about 40 to about 1000 μg / cm 2 , about 40 to about 500 μg / cm 2 , about 40~about 450μg / cm 2 , about 40~about 400μg / cm 2 , about 40~350μg / cm 2 , about 40 to about 300 μg / cm 2 , about 40 to about 250 μg / cm 2 , about 40 to about 200 μg / cm 2 , about 40 to about 190 μg / cm 2 , about 40 to about 180 μg / cm 2 , about 40 to about 170 μg / cm 2 , about 40 to about 160 μg / cm 2 , about 40 to about 150 μg / cm 2 , about 40 to about 140 μg / cm 2 , about 40 to about 130 μg / cm 2 , about 40 to about 120 μg / cm 2 , about 40 to about 110 μg / cm 2, about 40 to about 100 μg / cm 2 , about 40 to about 90 μg / cm 2 , about 40 to about 80 μg / cm 2 , about 40 to about 70 μg / cm 2 , about 40 to about 60 μg / cm 2 , about 40~50μg / cm 2 , about 50~about 2000μg / cm 2 , about 50~about 1500μg / cm 2 , about 50~about 1000μg / cm 2 , about 50~500μg / cm 2 , about 50~about 450μg / cm 2 , about 50~about 400μg / cm 2 , about 50~350μg / cm 2 , about 50~300μg / cm 2 , about 50~about 250μg / cm 2 , about 50~about 200μg / cm 2 , about 50~about 190μg / cm 2 , about 50~about 180μg / cm 2 , about 50~about 170μg / cm 2 , about 50~about 160μg / cm 2 , about 50~150μg / cm 2 , about 50~about 140μg / cm 2 , about 50~about 130μg / cm 2 , about 50~120μg / cm 2 , about 50~about 110μg / cm 2 , about 50~100μg / cm 2 , about 50~about 90μg / cm 2 , about 50~80μg / cm 2 , about 50~70μg / cm 2 , about 50~60μg / cm 2 , about 60~about 2000μg / cm 2 , about 60~about 1500μg / cm 2 , about 60~about 1000μg / cm 2 , about 60~500μg / cm 2 , about 60~about 450μg / cm 2 , about 60~about 400μg / cm 2 , about 60~350μg / cm 2, about 60~300μg / cm 2 , about 60~about 250μg / cm 2 , about 60~about 200μg / cm 2 , about 60 to about 190 μg / cm 2 , about 60~about 180μg / cm 2 , about 60~170μg / cm 2 , about 60 to about 160 μg / cm 2 , about 60~150μg / cm 2 , about 60~about 140μg / cm 2 , about 60~about 130μg / cm 2 , about 60~120μg / cm 2 , about 60~about 110μg / cm 2 , about 60~100μg / cm 2 , about 60~about 90μg / cm 2 , about 60~80μg / cm 2 , about 60~70μg / cm 2 , about 70~about 2000μg / cm 2 , about 70~about 1500μg / cm 2 , about 70~about 1000μg / cm 2 , about 70~500μg / cm 2 , about 70~about 450μg / cm 2 , about 70~about 400μg / cm 2 , about 70~350μg / cm 2 , about 70~300μg / cm 2 , about 70~about 250μg / cm 2 , about 70~about 200μg / cm 2 , about 70~about 190μg / cm 2 , about 70~180μg / cm 2 , about 70~about 170μg / cm 2 , about 70 to about 160 μg / cm 2 , about 70~150μg / cm 2 , about 70 to about 140 μg / cm 2 , about 70~about 130μg / cm 2 , about 70 to about 120 μg / cm 2 , about 70 to about 110 μg / cm 2 , about 70~100μg / cm 2 , about 70~about 90μg / cm 2, about 70~80μg / cm 2 , about 80~about 2000μg / cm 2 , about 80~about 1500μg / cm 2 , about 80~about 1000μg / cm 2 , about 80~500μg / cm 2 , about 80~about 450μg / cm 2 , about 80~about 400μg / cm 2 , about 80~about 350μg / cm 2 , about 80~300μg / cm 2 , about 80~about 250μg / cm 2 , about 80~about 200μg / cm 2 , about 80~about 190μg / cm 2 , about 80~180μg / cm 2 , about 80~about 170μg / cm 2 , about 80~about 160μg / cm 2 , about 80~150μg / cm 2 , about 80~about 140μg / cm 2 , about 80~about 130μg / cm 2 , about 80~120μg / cm 2 , about 80~about 110μg / cm 2 , about 80~100μg / cm 2 , about 80~90μg / cm 2 , about 90~about 2000μg / cm 2 , about 90~about 1500μg / cm 2 , about 90~1000μg / cm 2 , about 90~500μg / cm 2 , about 90~about 450μg / cm 2 , about 90~about 400μg / cm 2 , about 90~about 350μg / cm 2 , about 90~300μg / cm 2 , about 90~about 250μg / cm 2 , about 90~about 200μg / cm 2 , about 90~about 190μg / cm 2 , about 90 to about 180 μg / cm 2 , about 90 to about 170 μg / cm 2 , about 90 to about 160 μg / cm 2, about 90~150μg / cm 2 , about 90 to about 140 μg / cm 2 , about 90 to about 130 μg / cm 2 , about 90 to about 120 μg / cm 2 , about 90 to about 110 μg / cm 2 , about 90~100μg / cm 2 , about 100~about 2000μg / cm 2 , about 100~about 1500μg / cm 2 , about 100~about 1000μg / cm 2 , about 100~500μg / cm 2 , about 100~about 450μg / cm 2 , about 100~about 400μg / cm 2 , about 100~about 350μg / cm 2 , about 100~300μg / cm 2 , about 100~about 250μg / cm 2 , about 100~about 200μg / cm 2 , about 100~about 190μg / cm 2 , about 100~about 180μg / cm 2 , about 100~about 170μg / cm 2 , about 100 to about 160 μg / cm 2 , about 100~about 150μg / cm 2 , about 100~about 140μg / cm 2 , about 100~about 130μg / cm 2 , about 100~about 120μg / cm 2 , about 100~about 110μg / cm 2 , about 110~about 2000μg / cm 2 , about 110~about 1500μg / cm 2 , about 110~about 1000μg / cm 2 , about 110~500μg / cm 2 , about 110~about 450μg / cm 2 , about 110~about 400μg / cm 2 , about 110~about 350μg / cm 2 , about 110~about 300μg / cm 2 , about 110~about 250μg / cm 2 , about 110~about 200μg / cm 2 , about 110~about 190μg / cm2 , about 110~about 180μg / cm 2 , about 110~about 170μg / cm 2 , about 110~about 160μg / cm 2 , about 110~about 150μg / cm 2 , about 110~about 140μg / cm 2 , about 110~about 130μg / cm 2 , about 110~about 120μg / cm 2 , about 120~about 2000μg / cm 2 , about 120~about 1500μg / cm 2 , about 120~about 1000μg / cm 2 , about 120~about 500μg / cm 2 , about 120~about 450μg / cm 2 , about 120~about 400μg / cm 2 , about 120~about 350μg / cm 2 , about 120~300μg / cm 2 , about 120~about 250μg / cm 2 , about 120~about 200μg / cm 2 , about 120~about 190μg / cm 2 , about 120~about 180μg / cm 2 , about 120~about 170μg / cm 2 , about 120~about 160μg / cm 2 , about 120~about 150μg / cm 2 , about 120~about 140μg / cm 2 , about 120~about 130μg / cm 2 , about 130~about 2000μg / cm 2 , about 130~about 1500μg / cm 2 , about 130~about 1000μg / cm 2 , about 130~about 500μg / cm 2 , about 130~about 450μg / cm 2 , about 130~about 400μg / cm 2 , about 130~350μg / cm 2 , about 130~300μg / cm 2 , about 130~about 250μg / cm 2 , about 130~about 200μg / cm 2 , about 130~about 190μg / cm 2, about 130~about 180μg / cm 2 , about 130~about 170μg / cm 2 , about 130~about 160μg / cm 2 , about 130~about 150μg / cm 2 , about 130~about 140μg / cm 2 , about 140~about 2000μg / cm 2 , about 140~about 1500μg / cm 2 , about 140~about 1000μg / cm 2 , about 140~500μg / cm 2 , about 140~about 450μg / cm 2 , about 140~about 400μg / cm 2 , about 140~about 350μg / cm 2 , about 140~about 300μg / cm 2 , about 140~about 250μg / cm 2 , about 140~about 200μg / cm 2 , about 140~about 190μg / cm 2 , about 140~about 180μg / cm 2 , about 140~about 170μg / cm 2 , about 140~about 160μg / cm 2 , about 140~about 150μg / cm 2 , about 150~about 2000μg / cm 2 , about 150~about 1500μg / cm 2 , about 150~about 1000μg / cm 2 , about 150~500μg / cm 2 , about 150~about 450μg / cm 2 , about 150~about 400μg / cm 2 , about 150~350μg / cm 2 , about 150~300μg / cm 2 , about 150~about 250μg / cm 2 , about 150~200μg / cm 2 , about 150~about 190μg / cm 2 , about 150~about 180μg / cm 2 , about 150~about 170μg / cm 2 , about 150~about 160μg / cm 2 , about 160~about 2000μg / cm 2, about 160~about 1500μg / cm 2 , about 160~about 1000μg / cm 2 , about 160~about 500μg / cm 2 , about 160~about 450μg / cm 2 , about 160~about 400μg / cm 2 , about 160~350μg / cm 2 , about 160~300μg / cm 2 , about 160~about 250μg / cm 2 , about 160~about 200μg / cm 2 , about 160~about 190μg / cm 2 , about 160~about 180μg / cm 2 , about 160~about 170μg / cm 2 , about 170~about 2000μg / cm 2 , about 170~about 1500μg / cm 2 , about 170~about 1000μg / cm 2 , about 170~about 500μg / cm 2 , about 170~about 450μg / cm 2 , about 170~about 400μg / cm 2 , about 170~350μg / cm 2 , about 170~300μg / cm 2 , about 170~about 250μg / cm 2 , about 170~200μg / cm 2 , about 170~about 190μg / cm 2 , about 170~about 180μg / cm 2 , about 180~about 2000μg / cm 2 , about 180~about 1500μg / cm 2 , about 180~about 1000μg / cm 2 , about 180~about 500μg / cm 2 , about 180~about 450μg / cm 2 , about 180~about 400μg / cm 2 , about 180~350μg / cm 2 , about 180~300μg / cm 2 , about 180~about 250μg / cm 2 , about 180~200μg / cm 2 , about 180~about 190μg / cm 2, about 190~about 2000μg / cm 2 , about 190~about 1500μg / cm 2 , about 190~about 1000μg / cm 2 , about 190~about 500μg / cm 2 , about 190~about 450μg / cm 2 , about 190~about 400μg / cm 2 , about 190~350μg / cm 2 , about 190~300μg / cm 2 , about 190~about 250μg / cm 2 , about 190~200μg / cm 2 , about 200~about 2000μg / cm 2 , about 200~about 1500μg / cm 2 , about 200~about 1000μg / cm 2 , about 200~500μg / cm 2 , about 200~about 450μg / cm 2 , about 200~about 400μg / cm 2 , about 200~350μg / cm 2 , about 200~300μg / cm 2 , about 200~about 250μg / cm 2 , about 250~about 2000μg / cm 2 , about 250~about 1500μg / cm 2 , about 250~about 1000μg / cm 2 , about 250~500μg / cm 2 , about 250~about 450μg / cm 2 , about 250~about 400μg / cm 2 , about 250~350μg / cm 2 , about 250~300μg / cm 2 , about 300~about 2000μg / cm 2 , about 300~about 1500μg / cm 2 , 300~about 1300μg / cm 2 , about 300~about 1000μg / cm 2 , about 300~500μg / cm 2 , about 300~450μg / cm 2 , about 300~400μg / cm 2 , about 300~350μg / cm 2, about 350 to about 2000μg / cm 2 , about 350 to about 1500μg / cm 2 , about 350 to about 1000μg / cm 2 , about 350 to about 500μg / cm 2 , about 350 to about 450μg / cm 2 , about 350 to about 400μg / cm 2 , about 400 to about 2000μg / cm 2 , about 400 to about 1500μg / cm 2 , about 400 to about 1000μg / cm 2 , about 400 to about 500μg / cm 2 , about 400 to about 450μg / cm 2 , about 450 to about 2000μg / cm 2 , about 450 to about 1500μg / cm 2 , about 450 to about 1000μg / cm 2 , about 450~500μg / cm 2 , about 500 to about 2000μg / cm 2 , about 500 to about 1500μg / cm 2 , about 500 to about 1000μg / cm 2 , about 1000~2000μg / cm 2 , about 1000~1500μg / cm 2 , about 1500~2000μg / cm 2 , or about 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 500, 1000, 1100, 1200, 1300, 1400, 150 0 young Or 200μg / cm 2 or more.

[0141] In any of the foregoing embodiments, the active composition may be in liquid or solid form. By way of example and not limitation, the active composition may be in the form of a cream, lotion, eye drop, ear drop, sinus rinse, nasal, oral mucosa, skin or foot treatment spray, ointment, deodorant, body wash, shampoo, scalp treatment, mouthwash, toothpaste, lozenge, beverage, capsule, lubricant, or powder, such as produced by spray drying the nanoemulsion (or microemulsion) of the present disclosure. In some embodiments, the active composition further comprises a carrier formulation. Thus, in some embodiments, the nanoemulsion (or microemulsion) of the present disclosure may not include any exogenous additives having surfactant and / or emulsifier properties not naturally occurring in oils in amounts sufficient to enhance the stability of the droplets or particles, any exogenous additives having thickening or crystallization-inhibiting properties not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts, and the carrier formulation may include these agents. By way of example and not limitation, the active composition can be formulated as a cream that may require thickening agents or other agents, but the nanoemulsion (or microemulsion) component can be free of such agents in some embodiments. In some embodiments, the active composition does not include any exogenous additives with surfactant and / or emulsifier properties not naturally occurring in oils in amounts sufficient to enhance droplet or particle stability, any exogenous additives with thickening or crystallization-inhibiting properties not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts.

[0142] In any of the foregoing embodiments, the active composition may contain from about 1% to about 15% by weight of the total weight of the active composition of the disclosed composition including oil. By way of example and not limitation, the disclosed composition may contain from about 1% to about 15% by weight, from about 2% to about 15% by weight, from about 3% to about 15% by weight, from about 4% to about 15% by weight, from about 5% to about 15% by weight, from about 10% to about 15% by weight, from about 1% to about 10% by weight, from about 2% to about 10% by weight, from about 3% to about 10% by weight, from about 4% to about 10% by weight, from about 5% to about 10% by weight, from about 1% to about 5 ... %, about 2% to about 5% by weight, about 3% to about 5% by weight, about 4% to about 5% by weight, about 1% to about 4% by weight, about 2% to about 4% by weight, about 3% to about 4% by weight, about 1% to about 3% by weight, about 2% to about 3% by weight, about 1% to about 2% by weight, or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 15% by weight.

[0143] In some embodiments, a method for administering an active ingredient to a subject is provided, comprising administering to the subject an active composition of any of the above embodiments. By way of example and not limitation, the administering step can be performed orally, by injection, e.g., intravenously, intramuscularly, intrathecally, or subcutaneously, sublingually, buccally, rectally, intravaginally, ocularly, aurally, nasally, e.g., by spray, inhalation, e.g., via aerosol, skin, e.g., topically, implanted, transdermally, or systemically.

[0144] In some embodiments, a method for preparing an active composition of the present disclosure is provided, comprising combining an active ingredient with an oil to form an emulsion, thereby obtaining the active ingredient in the oil of the active composition of the present disclosure. It should be understood that the active ingredient can be added to the oil before forming the emulsion, or to the composition after forming the emulsion, and the emulsion can have the properties of the nanoemulsions and microemulsions of the present disclosure. By way of example and without limitation, a method for preparing an active composition of the present disclosure can include providing an oil of the present disclosure, combining the oil and the active ingredient, providing a polar liquid, combining the oil and the polar liquid to form an emulsion premix, and forming an emulsion from the nanoemulsion premix. Alternatively, the active ingredient can be added after the formation of the nanoemulsion or microemulsion. By way of further example and without limitation, the emulsion can be a nanoemulsion or microemulsion as described in the present disclosure. The method for forming the emulsion can be any method known in the art or described in the present disclosure. It should be understood that the method of preparing the active composition of the present disclosure can further include, in certain aspects, adding a carrier formulation to the active composition. In some embodiments, the nanoemulsion (or microemulsion) can be free of any exogenous additives with surfactant and / or emulsifier properties not naturally occurring in oils in sufficient amounts to enhance the stability of the droplets or particles, any exogenous additives with thickening or crystallization-inhibiting properties not naturally occurring in oils in sufficient amounts to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts, and the carrier formulation can include these agents. By way of example and not limitation, the active composition can be further formulated into a cream that may require thickening agents or other agents, but the nanoemulsion (or microemulsion) components can be free of such agents in some embodiments.In some embodiments, the active composition does not include any exogenous additives that have surfactant and / or emulsifier properties that are not naturally occurring in oils in amounts sufficient to enhance droplet or particle stability, any exogenous additives that have thickening or crystallization-inhibiting properties that are not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts.

[0145] In some embodiments, the active composition can include a first component comprising a nanoemulsion (or microemulsion) of the present disclosure and a second component comprising a carrier formulation. In such embodiments, the first component can further comprise an active ingredient, which can be present in the oil of the nanoemulsion (or microemulsion) of the present disclosure. Alternatively, the active ingredient can be present in the aqueous phase of the nanoemulsion or microemulsion. In some embodiments, the nanoemulsion (or microemulsion) can include any exogenous additives with surfactant and / or emulsifier properties not naturally occurring in the oil in an amount sufficient to enhance the stability of the droplets or particles, any exogenous additives with thickening or crystallization-inhibiting properties not naturally occurring in the oil in an amount sufficient to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts, and the carrier formulation can include these agents. By way of example and not limitation, the active composition can be further formulated into a cream that may require thickening agents or other agents, but the nanoemulsion (or microemulsion) component can be free of such agents in some embodiments. In some embodiments, the active composition does not include any exogenous additives with surfactant and / or emulsifier properties not naturally occurring in oils in amounts sufficient to enhance droplet or particle stability, any exogenous additives with thickening or crystallization-inhibiting properties not naturally occurring in oils in amounts sufficient to thicken the composition or inhibit crystal formation, respectively, polyhydric alcohols, or bile salts.

[0146] Treatment method In some embodiments, a method for treating or preventing acne in a subject in need thereof may comprise administering to the subject an active composition of the present disclosure, wherein the active ingredient is administered in a therapeutically effective amount suitable for treating or preventing acne, hi some embodiments, the active ingredient is salicylic acid.

[0147] In some embodiments, a method for treating or preventing pain in a subject in need thereof may comprise administering to the subject an active composition of the present disclosure, wherein the active ingredient is administered in a therapeutically effective amount and is suitable for treating or preventing pain, hi some embodiments, the active ingredient is lidocaine, prilocaine, bupivacaine, or a combination thereof.

[0148] In some embodiments, a method for treating or preventing inflammation in a subject in need thereof may comprise administering to the subject an active composition of the present disclosure, wherein the active ingredient is administered in a therapeutically effective amount and is suitable for treating or preventing inflammation. In some embodiments, the active ingredient is diclofenac, cannabidiol, aspartyl-alanyl-diketopiperazine, hydrocortisone, or a combination thereof.

[0149] In some embodiments, a method for treating or preventing cancer in a subject in need thereof can include administering to the subject an active composition of the present disclosure, wherein the active ingredient is administered in a therapeutically effective amount suitable for treating or preventing cancer. In some embodiments, the active ingredient is 5-fluorouracil.

[0150] In some embodiments, a method for administering an anti-aging compound or vitamin to a subject in need thereof can include administering to the subject an active composition of the present disclosure, wherein the active ingredient is a therapeutically effective amount. In some embodiments, the active ingredient is trifluoroacetyl tripeptide-2, hexapeptide-11, retinol, or retinyl palmitate.

[0151] It should be understood that the disclosure herein is not limited to the use of EMO and FFA oils, and any oil meeting the requirements of this disclosure may be used. EXAMPLES

[0152] In the examples below, unless otherwise stated, the MAG, DAG, TAG and FFA content and fatty acid profile may be as set forth in Table 1 below, or in the preceding tables of fatty acid content and exemplary EMOs herein. In general, unless otherwise stated, it can be assumed that an FFA oil is >90% FFA, typically about 93% + / - 2%.

[0153] Preparation of fatty acid oil Unless otherwise specified, the fatty acid oil in the following examples (except Example 1) was prepared by the following procedure. For all examples, the FFA oil was assumed to contain 93% + / - 2% FFA, except for the fish FFA oil, which contains 77% + / - 2% FFA, and the algae FFA oil, which contains 61% + / - 2% FFA. However, longer reaction times and different conditions can result in higher FFA, if necessary. As used herein, it should be understood that for each composition, the nomenclature is n(oil)-non-FFA% when derived from a single oil source, and n(EMO) / (FFA)-EMO%. For example, an oil made with sesame EMO and FFA oil to produce a total of 50% FFA is nS50, and an oil made with sesame EMO and FFA oil to produce a total of 75% FFA is nS25. Additionally, an oil made with 25% oat EMO and 75% flaxseed FFA oil is nOa / Fx-25, the combination being on a weight basis.

[0154] The fatty acid oil was prepared by complete hydrolysis of triacylglycerides (TAGs) in the crude oil to free fatty acids (FFAs) and glycerol, followed by separation of the FFAs and glycerol.

[0155] Free fatty acid (FFA) oil preparation Free fatty acid oil was prepared by complete hydrolysis of TAG to FFA and glycerol, followed by separation of glycerol from the FFA oil. FFA oil was prepared in a 5 L stirred jacketed glass reactor. Citrate buffer (100 mM, pH 5.8) was prepared by combining 18.5 grams of food grade citric acid and 1.50 g of food grade sodium hydroxide in 963 mL of distilled deionized water. Amano Lipase AY (0.78 g) was dissolved in the solution, which was then heated to 33° C. and stirred at 300 rpm. After a brief (10 min) period of vacuum degassing, 780 g of starting oil was added to the reactor. The reaction volume was blanketed with nitrogen and the reaction was allowed to proceed for 24 hours until all TAG was converted to fatty acids and glycerol. Once the reaction was complete, the mixture was heated to 70° C. for 1 hour to inactivate the lipase. The stirring was stopped. After the two phases separated, the upper phase (free fatty acid oil) was removed and stored at 4 °C in an opaque plastic bottle under nitrogen. The components of the oil samples were separated using TLC plates (Analtech Uniplate silica gel GHL with inorganic binder, 20 × 20 cm, 250 μm). The solvent was a hexane:diethyl ether:acetic acid (70:30:1) solution. Typical sample size was 0.2 μL. After the solvent front reached near the top of the plate (approximately 1 cm), the plate was removed from the TLC tank and the solvent was allowed to evaporate in a fume hood. The components were visualized by iodine vapor in the TLC tank (at room temperature) and relative intensity estimated by colorimetric imaging (Amersham 600 Imager). After 15 min in the tank, the plate was removed and photographed. The intensity of the spots decreased after 30–60 min.

[0156] Preparation of enzyme-modified oil (EMO) The enzyme-modified oil was produced from the FFA oil by selectively re-esterifying the FFAs to glycerol to form MAGs and (to a much lesser extent) DAGs. The above FFA oil was combined with 1,560 g of food-grade glycerol and heated to 30° C. with stirring (300 rpm). A vacuum was applied (approximately 720 mmHg) to degas the material and remove residual water. Amano Lipase G (1.56 g in 50 mL DI water) was then added to the reactor and the vacuum was reapplied (approximately 740 mmHg). The reaction was allowed to proceed for 72 hours and progress was monitored by TLC. Once the level of FFAs had dropped below 20%, the reaction was stopped by removing the vacuum, blanketing the reactor with nitrogen, and heating the system to 70° C. for 1 hour to inactivate the enzymes. The fatty acid concentrations were measured by titration. The samples were dissolved in a solvent (95% ethanol / diethyl ether, 1 / 1, v / v) and titrated to neutrality (indicated by phenolphthalein) with 0.1 M KOH in ethanol. Salt (sodium chloride) was then added to the reactor. Once the salt was suspended, the stirring was stopped. After the two phases separated (approximately 3 hours), the upper phase (EMO) was removed. An antioxidant (tocopherol, 200 ppm) was added and the material was stored at 4 °C in an opaque plastic bottle under nitrogen.

[0157] Analysis of EMO was performed using a previously described HPLC method (Bruno Lima dos Santos, Kissya Kropf da Silva, Amanda Pereira Franco dos Santos, Debora Franca de Andrade & Luiz Antonio d'Avila(2016)Simultaneous analysis of esters and acylglycerols in biodiesel by high-performance liquid chromatography with refractive index detection,Journal of Liquid Chromatography & Related Technologies,39:13,620-626,DOI:10.1080 / 10826076.2016.1225221).

[0158] The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and a RID-10A refractive index detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 20 uL, isocratic elution with a mobile phase consisting of 85% methanol, 10% isopropanol, and 5% hexane, a flow rate of 0.800 mL / min, and a column temperature of 40° C. The column used was a SUPELCOSIL LC-18 column (250 mm×4.6 mm, 5 um particle size). Samples were prepared in the mobile phase. Mobile phase blank chromatograms were used to correct the background.

[0159] In general, retention times were 3.4-4.0 min for glycerol, 4.0-6.2 min for MAG and FFA, 6.3-10.8 min for DAG, and 11.0-50.0 min for TAG.

[0160] Integration of these peaks provided the relative ratios, or area percentages, of glycerol, MAG+FFA, DAG, and TAG.

[0161] Because the MAG and FFA peaks overlap, the FFA content was determined by titration. Samples were dissolved in solvent (95% ethanol / diethyl ether, 1 / 1, v / v) and titrated to neutral (represented by phenolphthalein) with 0.1 M KOH in ethanol. The values ​​are reported as weight percent.

[0162] MAG content was calculated by subtracting the FFA content from MAG+FFA determined by HPLC.

[0163] Table 1 below provides the relative glycerol, MAG, DAG, TAG, and FFA contents of the resulting EMO used in the following examples unless otherwise stated. [Table 4]

[0164] Nanoemulsion Preparation Nanoemulsions were prepared from either EMO or a combination of EMO and FFA oils. 1.5 g of total oil was weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high-sheer homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power.

[0165] Example 1: Production of almond fatty acid oil and enzyme modified oil (EMO) The fatty acid oil was prepared by complete hydrolysis of TAG to FFA and glycerol followed by separation. Almond fatty acid oil was prepared in a 20 L stirred jacketed glass reactor. Citrate buffer (100 mM, pH 5.8) was prepared by combining 133 grams of food grade citric acid and 75 g of food grade sodium hydroxide in 7,000 mL of distilled deionized water. Amano Lipase AY (5.8 g) was dissolved in the solution, which was then heated to 33° C. and stirred at 300 rpm. After a brief (10 min) vacuum degassing, 5,600 g of almond oil was added to the reactor. The reaction volume was blanketed with nitrogen and the reaction was allowed to proceed for 12 hours until all TAG was converted to fatty acids and glycerol.

[0166] Once the reaction was complete, the mixture was heated to 70°C for 1 hour to inactivate the lipase. Stirring was stopped. After the two phases separated, the top phase (fatty acid oil) was removed and stored at room temperature in an opaque plastic bottle under nitrogen.

[0167] The components of the oil samples were separated using TLC plates (Analtech Uniplate silica gel GHL with inorganic binder, 20 × 20 cm, 250 μm). The solvent was a hexane:diethyl ether:acetic acid (70:30:1) solution. Typical sample size was 0.2 μL. After the solvent front reached near the top of the plate (approximately 1 cm), the plate was removed from the TLC tank and the solvent was allowed to evaporate in a fume hood. The components were visualized by iodine vapor in the TLC tank (at room temperature) and relative intensity estimated by colorimetric imaging (Amersham 600 Imager). After 15 min in the tank, the plate was removed and photographed. The intensity of the spots decreased after 30–60 min.

[0168] EMO was produced from fatty acid oil by selectively re-esterifying FFA to glycerol to form MAG and (to a much lesser extent) DAG. The fatty acid oil was combined with 10,260 g of food grade glycerol and heated to 30° C. with stirring (300 rpm). A vacuum was applied (approximately 720 mmHg) to degas the material and remove residual water. Amano Lipase G (5 g in 50 mL DI water) was then added to the reactor and the vacuum was reapplied (approximately 740 mmHg). The reaction was allowed to proceed for 72 hours and progress was monitored by TLC.

[0169] Once the level of FFAs had fallen below 15%, the reaction was stopped by removing the vacuum, blanketing the reactor with nitrogen, and heating the system to 70° C. for 1 h to inactivate the enzyme.

[0170] Fatty acid concentrations were measured by titration: samples were dissolved in solvent (95% ethanol / diethyl ether, 1 / 1, v / v) and titrated to neutral (indicated by phenolphthalein) with 0.1 M KOH in ethanol.

[0171] Salt (sodium chloride) was then added to the reactor. Once the salt was suspended, the stirring was stopped. After the two phases separated (3 hours), the top phase (acylglycerol oil) was removed. Antioxidant (tocopherol, 200 ppm) was added and the material was stored at room temperature in an opaque plastic bottle under nitrogen.

[0172] Lipid components including C10:0 capric acid, C12:0 lauric acid, C14:0 myristic acid, C16:0 palmitic acid, C18:0 stearic acid, C18:1 oleic acid, C18:2 linoleic acid, and C18:3 alpha-linolenic acid were analyzed after derivatization as fatty acid methyl esters and compared with standards. For derivatization, samples (500 μl) were added to 5 ml reaction tubes containing 2 ml of boron trifluoride solution (12% in methanol), 20 μl of dimethoxypropane, and 100 μl of tridecanoic acid internal standard solution (10 mg / ml). The reaction tubes were vortexed and incubated in a heating block at 60° C. for 30 min.

[0173] The reaction tube was removed from the heating block and allowed to cool for 15 minutes. The reaction was then quenched by adding 1 ml of distilled water, followed by 1 ml of hexane. The reaction tube was vortexed for 60 seconds and the phases were allowed to separate for 3 minutes. The upper (hydrophobic) phase was removed to a 1.5 ml tube containing approximately 50 mg of sodium sulfate (anhydrous). After vortexing for 60 seconds, the 1.5 ml tube was centrifuged and approximately 500 μl of the clear, dry hydrophobic phase was transferred to a gas chromatography sample vial.

[0174] Samples were analyzed using an Agilent 7890A Gas Chromatograph with a flame ionization detector and Agilent Openlab CDS Chemstation software. GC column: Omegawax100 (15m x 0.1mm x 0.1um) column. Results were converted to weight percent based on an internal standard.

[0175] MCT, canola and almond oils were processed according to the manufacturing methods of the present disclosure, and the fatty acid profile of each was measured in both the starting oil and the MAG oil, as shown in Table 2 below.

[0176] As shown, both the starting oil and the EMO contained essentially the same fatty acid profile.

[0177] Separate experiments were performed using almond and canola oils, yielding data in Table 3 showing the same results for oleic acid, linoleic acid, and linolenic acid. [Table 5] [Table 6]

[0178] These results demonstrate that the manufacturing process of the present disclosure can preserve the fatty acid profile of the starting oil in EMO, which differs from traditional "distilled" oils, whose fatty acid profile differs significantly from the starting oil based on the functional use of the distilled oil.

[0179] Example 2: Preparation of nanoemulsions from a single oil source Nanoemulsions were prepared from medium chain triglyceride (MCT) enzyme-modified oil as described above. Briefly, MCT oil was subjected to complete enzymatic hydrolysis to obtain an FFA oil containing free fatty acids, which was then further enzymatically treated in the presence of glycerol to re-esterify the FFAs to MAG and DAG, resulting in a processed oil containing 79% MAG and DAG, and 21% FFA.

[0180] To prepare the first nanoemulsion, 1.5 g of the treated MCT oil was weighed into a 50 mL beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. Using a high shear homogenizer, the mixture was subjected to high shear for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was processed for two cycles (5 minutes sonication / 2 minutes cooling) at 90% power.

[0181] Further nanoemulsions were prepared by combining the processed MCT oil (containing MAG and DAG) with the MCT FFA oil obtained after enzymatic hydrolysis to achieve various ratios of MAG and DAG to FFA, as shown in Table 4 below. These nanoemulsions were evaluated for Z-average droplet size, polydispersity index, and average zeta potential using a Zetasizer Ultra (Malvern Panalytical) according to the manufacturer's instructions. Measurements were performed in triplicate. [Table 7]

[0182] With the data obtained shown in Table 5 below, the corresponding process was carried out using olive oil. [Table 8]

[0183] With the data obtained shown in Table 6 below, the corresponding process was carried out using linseed oil. [Table 9]

[0184] With the data obtained shown in Table 7 below, the corresponding process was carried out using sesame oil. [Table 10]

[0185] FIG. 1 shows the Z-average size of droplets in nanoemulsions produced from four different starting oils as a function of %FFA.

[0186] With the data obtained shown in Table 8 below, the corresponding process was carried out using rosehip oil. [Table 11]

[0187] With the data obtained shown in Table 9 below, the corresponding process was carried out using hemp seed oil. [Table 12]

[0188] With the data obtained shown in Table 10 below, the corresponding process was carried out using sunflower oil. [Table 13]

[0189] With the data obtained shown in Table 11 below, the corresponding process was carried out using oat oil. [Table 14]

[0190] The above results demonstrate that nanoemulsions can be prepared from different starting oils utilizing different ratios of MAG and DAG and FFA. In some cases, only FFA oils can form nanoemulsions without the addition of enzyme-modified oils containing MAG and, to some extent, DAG. In all cases, the TAG content will be low or absent since the TAG from the starting oil has been substantially or completely hydrolyzed in the first processing step. It should be understood that when the oil in the nanoemulsion contains EMO, the EMO can be derived from a single starting oil source or from two, three or more starting oil sources. For example, the starting oil sources can be blended prior to enzyme processing to obtain EMO.

[0191] Example 3: Preparation of nanoemulsions from different oil sources Nanoemulsions from combinations of EMO and FFA oils from different oils in different ratios were prepared and analyzed as described above.

[0192] The data obtained for the combination of coconut EMO and MCT FFA oil is shown below in Table 12. [Table 15]

[0193] The data obtained for the combination of MCT EMO and coconut FFA oil is shown in Table 13 below. [Table 16]

[0194] The data obtained for the combination of fish EMO and flaxseed FFA oil is shown in Table 14 below. [Table 17]

[0195] The data obtained for the combination of flaxseed EMO and fish FFA oil is shown in Table 15 below. [Table 18]

[0196] The data obtained for the combination of fish EMO and coconut FFA oil is shown in Table 16 below. [Table 19]

[0197] The data obtained for the combination of flaxseed EMO and coconut FFA oil is shown in Table 17 below. [Table 20]

[0198] The data obtained for the combination of coconut EMO and flaxseed FFA oil is shown in Table 18 below. [Table 21]

[0199] The data obtained for the combination of coconut EMO and rosehip FFA oils is shown in Table 19 below. [Table 22]

[0200] The data obtained for the combination of rosehip EMO and coconut FFA oil is shown in Table 20 below. [Table 23]

[0201] The data obtained for the combination of rosehip EMO and flaxseed FFA oil is shown in Table 21 below.

[0202] [Table 24]

[0203] The data obtained for the combination of flaxseed EMO and rosehip FFA oil is shown in Table 22 below.

[0204] [Table 25]

[0205] The data obtained for the combination of algal EMO and linseed FFA oil is shown in Table 23 below.

[0206] [Table 26]

[0207] The data obtained for the combination of algal EMO and MCT FFA oil is shown in Table 24 below.

[0208] [Table 27]

[0209] The data obtained for the combination of oat EMO and flaxseed FFA oil is shown in Table 25 below.

[0210] [Table 28]

[0211] The data obtained for the combination of flaxseed EMO and oat FFA oil is shown in Table 26 below.

[0212] [Table 29]

[0213] Example 4: Stability of Nanoemulsions The nanoemulsions prepared in Examples 2 and 3 were stored at room temperature or refrigerated (4° C.). At various time points, samples were retested for Z-average particle size, polydispersity index, and zeta potential, as shown in the table below ("Fresh" refers to the starting nanoemulsion). [Table 30] [Table 31] [Table 32] [Table 33] [Table 34] [Table 35] [Table 36] [Table 37] [Table 38] [Table 39] [Table 40] [Table 41] [Table 42] [Table 43] [Table 44] [Table 45] [Table 46] [Table 47]

[0214] 2A-2S show the Z-average particle sizes of the nanoemulsions in Tables 27-44.

[0215] Example 5: Preparation of nanoemulsions from unmodified oils To evaluate the effect of TAG content on the production of nanoemulsions of the present disclosure, olive oil (unmodified TAG form) was mixed with olive FFA oil prepared as above in different ratios, and the mixture was prepared as a nanoemulsion according to the procedure described above. The Z-average particle size and polydispersity index were measured for these samples, and the results are provided in Table 45 below. [Table 48]

[0216] As shown in Table 45, olive oil, essentially TAG, alone was unable to form a nanoemulsion, as it resulted in the formation of two separate layers. Furthermore, the size of the droplets decreased with increasing FFA content and decreasing TAG content. Specifically, up to 50% olive oil (essentially TAG) still resulted in nanoemulsions with a Z-average size of less than 300 nm, while 60% olive oil resulted in larger particles, and the 100% TAG sample quickly separated into two layers.

[0217] Olive oil (unmodified TAG form) was blended with various ratios of MAG, several DAGs, and FFAs prepared as described above, as well as olive EMO containing nanoemulsions prepared therefrom as described above. The Z-average particle size and polydispersity index were measured for these samples, and the results are provided in Table 46 below. [Table 49]

[0218] As shown in Table 46, up to 80% of the TAG was still able to obtain a Z-average particle size below 300 nm.

[0219] The same procedure was carried out using olive oil (unmodified TAG form) blended with either oleic acid or glyceryl oleate in ratios of 75 / 25, 50 / 50 and 25 / 75. Two phases were obtained, whereas in the case of the blends no nanoemulsions were formed.

[0220] Example 6: Preparation of nanoemulsions using commercially available ingredients To evaluate nanoemulsions prepared from pre-made ingredients, nanoemulsions were prepared from various ratios of glyceryl oleate (MakingCosmetics, part #EMF-GLYOL-01) and / or oleic acid (Beantown Chemical, part #126125). The Z-average size and polydispersity index were measured as described above. The results are shown in Table 47 below. [Table 50]

[0221] These results can be compared to those in Table 5 for the Olive EMO nanoemulsion. In contrast, the glyceryl oleate / oleic acid nanoemulsion did not form a Z-average droplet size nanoemulsion below 300 nm. Both the 50 / 50 and 25 / 75 blends yielded creams, while the other samples yielded larger droplet sizes of about 600 nm or greater. Thus, as performed in this example, the commercial ingredients did not reproduce the results with EMO.

[0222] Example 7: Nanoemulsions from multiple oil sources Nanoemulsions were formed from EMO and FFA of rosehip, flaxseed and MCT oils as described in the previous examples. Size, PDI and Zeta potential data are shown in Table 48 below. [Table 51]

[0223] Nanoemulsions containing three different EMOs or three different EMOs plus the corresponding FFA in a 50 / 50 ratio achieved particle sizes below 300 nm and PDIs below 0.300.

[0224] Example 8: Amount of oil in nanoemulsion Nanoemulsions were prepared from Rosehip EMO at various % oil by total weight of the nanoemulsion. Table 49 below provides size and PDI data. [Table 52]

[0225] Rosehip EMO nanoemulsions could be formed when the weight percentage of oil was 1% to 30% of the total weight of the formulation. At 50% oil weight or more, a cream was formed.

[0226] Example 9: Production of a nanoemulsion containing CBD The fatty acid oil was prepared by complete hydrolysis of TAG to FFA and glycerol followed by separation. Almond fatty acid oil was prepared in a 20 L stirred jacketed glass reactor. Citrate buffer (100 mM, pH 5.8) was prepared by combining 133 grams of food grade citric acid and 75 g of food grade sodium hydroxide in 7,000 mL of distilled deionized water. Amano Lipase AY (5.8 g) was dissolved in the solution, which was then heated to 33° C. and stirred at 300 rpm. After a brief (10 min) vacuum degassing, 5,600 g of almond oil was added to the reactor. The reaction volume was blanketed with nitrogen and the reaction was allowed to proceed for 12 hours until all TAG was converted to fatty acids and glycerol.

[0227] Once the reaction was complete, the mixture was heated to 70°C for 1 hour to inactivate the lipase. Stirring was stopped. After the two phases separated, the top phase (fatty acid oil) was removed and stored at room temperature in an opaque plastic bottle under nitrogen.

[0228] The components of the oil samples were separated using TLC plates (Analtech Uniplate silica gel GHL with inorganic binder, 20 × 20 cm, 250 μm). The solvent was a hexane:diethyl ether:acetic acid (70:30:1) solution. Typical sample size was 0.2 μL. After the solvent front reached near the top of the plate (approximately 1 cm), the plate was removed from the TLC tank and the solvent was allowed to evaporate in a fume hood. The components were visualized by iodine vapor in the TLC tank (at room temperature) and relative intensity estimated by colorimetric imaging (Amersham 600 Imager). After 15 min in the tank, the plate was removed and photographed. The intensity of the spots decreased after 30–60 min.

[0229] EMO was produced from fatty acid oil by selectively re-esterifying FFAs to glycerol to form MAGs and (to a much lesser extent) DAGs. The fatty acid oil was combined with 10,260 g of food grade glycerol and heated to 30° C. with stirring (300 rpm). A vacuum was applied (approximately 720 mmHg) to degas the material and remove residual water. Amano Lipase G (5 g in 50 mL DI water) was then added to the reactor and the vacuum was reapplied (approximately 740 mmHg). The reaction was allowed to proceed for 72 hours and progress was monitored by TLC.

[0230] Once the level of FFAs had fallen below 10%, the reaction was stopped by removing the vacuum, blanketing the reactor with nitrogen, and heating the system to 70° C. for 1 h to inactivate the enzyme.

[0231] Fatty acid concentrations were measured by titration: samples were dissolved in solvent (95% ethanol / diethyl ether, 1 / 1, v / v) and titrated to neutral (indicated by phenolphthalein) with 0.1 M KOH in ethanol.

[0232] Salt (sodium chloride) was then added to the reactor. Once the salt was suspended, the stirring was stopped. After the two phases separated (3 hours), the top phase (acylglycerol oil) was removed. Antioxidant (tocopherol, 200 ppm) was added and the material was stored at room temperature in an opaque plastic bottle under nitrogen.

[0233] MMN was prepared by combining EMO with the cargo, CBD, and subsequent emulsification. CBD was chosen because it is essentially insoluble in water. The water solubility of cannabinoids averages approximately 0.0015 mg / mL, which is too low for efficient delivery to the body but high enough to cause rapid nanoemulsion destabilization by Ostwald ripening.

[0234] The cargo (2.5 g of 99.9% CBD isolate) was dissolved in 10 g of almond EMO (9.7% FFA) preheated to 50° C. in a 50 mL conical tube. The mixture was warmed overnight to ensure complete dissolution.

[0235] A coarse emulsion was prepared by adding 8.8 mL of warm (50° C.) EMO / CBD dropwise to 72 mL of warm (50° C.) deionized water in a 150 mL beaker. The mixture was stirred constantly for 5 minutes while the oil was added using a high shear homogenizer. The resulting product was a milky white coarse emulsion.

[0236] The coarse emulsion was then transferred to a QSonica Model Q700CA sonicator equipped with a 1 / 2 inch probe. The beaker was cooled in an ice bath and processed for 24 cycles (5 minutes sonication / 2 minutes cooling) and 90% power. This was sample 102919.1. The emulsion was then diluted 1 / 10 with water and subjected to 12 more cycles. This was sample 102919.1 3X.

[0237] The TAG / DAG / MAG / FFA ratios in the samples were estimated by TLC to give the following: [Table 53]

[0238] The size and zeta potential of the nanoemulsions were measured using a Zetasizer Ultra (Malvern Panalytical) (102919.1 3X). A disposable sizing cell and a disposable folded capillary cell were used for size and zeta potential measurements (in triplicates), respectively. As shown in Figure 3, the average size of the particles was determined to be 163 nm, well below the target size of <300 nm.

[0239] The zeta potential of MMN (102919.1 3X) was also determined, as shown in Figure 4. As shown, the zeta potential of the particles was measured to be -44.4 + / - 0.9 mV, well below the target of at least -30 mV.

[0240] Example 10: Preparation of nanoemulsions containing CBD In another experiment, 4.0 g of 99.9% CBD isolate was dissolved in 16 g of almond EMO, prepared as described in Example 9, pre-heated to 50° C. in a 50 mL conical tube. The mixture was warmed to 50° C. to ensure complete dissolution.

[0241] A coarse emulsion was prepared by adding 10 mL of the warm (50° C.) EMO / CBD mixture dropwise to 90 mL of warm (50° C.) deionized water in a 150 mL beaker while the beaker was cooled in an ice bath and sonicated with a QSonica Model Q700CA sonicator equipped with a ½ inch probe for 12 cycles (5 min sonication / 2 min cooling) and 90% power. This produced a milky white coarse emulsion.

[0242] The coarse emulsion was then subjected to 65 or more sonication cycles (approximately 6 hours).

[0243] The resulting nanoemulsion (111819.1) was found to be stable with an average particle size of 169.2 nm and a zeta potential of -42.6 mV. Size distribution measurements were performed in triplicate. The size distribution of the nanoemulsion is shown in Figure 5.

[0244] Example 11: Preparation of nanoemulsion using canola oil and vitamin E MMN is prepared according to the procedure described above in Example 9 using canola oil as the starting oil instead of almond oil and vitamin E as the cargo instead of CBD. MMN is also prepared according to the procedure described above in Example 9 using almond oil with vitamin E as the cargo. Similar results are expected to be obtained.

[0245] Example 12: Comparison of EMO nanoemulsion, EMO microemulsion, and TAG microemulsion for enhancing drug permeation through the skin The permeation profile of hydrocortisone across a synthetic skin-like membrane (Strat-M®) was evaluated when different emulsion formats were formulated, including sesame EMO nanoemulsion (nS50) and microemulsion (micro-S50) and sesame TAG nanoemulsion (nano-TAG).

[0246] Sesame EMO nanoemulsions were prepared from a combination of sesame EMO and FFA oil in different ratios. The content of EMO oil is provided in Table 1, and the FFA oil was essentially 100% FFA. For nS25, sesame EMO (0.426 g) and sesame FFA oil (1.07 g) were weighed into a 50 mL metal beaker and heated to 60° C. Hydrocortisone (15 mg) (Acros Organics) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer (Brinkmann homogenizer model PT 10 / 35) for 30 seconds, resulting in a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 222 ± 7 nm, PDI = 0.175 ± 0.017).

[0247] nS50 was prepared using the same procedure as above with sesame EMO (0.852 g) and sesame FFA (0.648 g). The resulting nanoemulsion was analyzed by DLS (Z average = 185 ± 5 nm, PDI = 0.181 ± 0.013).

[0248] nS75 was prepared using the same procedure as above with sesame EMO (1.278 g) and sesame FFA (0.222 g). The resulting nanoemulsion was analyzed by DLS (Z average = 179 ± 1 nm, PDI = 0.203 ± 0.010).

[0249] Oat / linseed EMO nanoemulsions were prepared from a combination of oat EMO and linseed FFA oil in different ratios. The content of EMO oil is provided in Table 1, and the FFA oil was essentially 100% FFA. For nOa / Fx25, oat EMO (0.375 g) and linseed FFA oil (1.125 g) were weighed into a 50 mL metal beaker and heated to 60° C. Hydrocortisone (15 mg) (Acros Organics) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated with 2 cycles (5 min sonication / 2 min cooling) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 181 ± 3 nm, PDI = 0.157 ± 0.013). nOa / Fx75 was prepared using the same procedure as above with oat EMO (1.125 g) and linseed FFA (0.375 g). The resulting nanoemulsion was analyzed by DLS (Z average = 160 ± 3 nm, PDI = 0.194 ± 0.019). nOa / Fx50 was prepared using the same procedure as above with oat EMO (0.750 g) and linseed FFA (0.750 g). The resulting nanoemulsion was analyzed by DLS (Z average = 172 ± 3 nm, PDI = 0.165 ± 0.041). nFx0 was prepared using the same procedure as above with flaxseed FFA (1.500 g). The resulting nanoemulsion was analyzed by DLS (Z average = 193 ± 1 nm, PDI = 0.147 ± 0.032).

[0250] Sesame EMO microemulsion (micro-S50) was prepared from a combination of sesame EMO and FFA oil. Sesame EMO (0.852 g) and sesame FFA oil (0.648 g) were weighed into a 50 mL metal beaker and heated to 60°C. Hydrocortisone (15 mg) was added to the oil mixture and mixed gently at 60°C to form a fine dispersion. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60°C) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0251] TAG nanoemulsion (nano-TAG sesame) was prepared from a combination of unmodified sesame oil and span80. Sesame oil (1.5 g) and span80 (0.75 g) were weighed into a 50 mL metal beaker and heated to 60° C. Hydrocortisone (15 mg) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 12.75 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was sonicated for 5 minutes at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 262 ± 1 nm, PDI = 0.230 ± 0.007).

[0252] The properties of the various formulations are provided in Table 51 below. [Table 54]

[0253] A free drug control was prepared by dissolving hydrocortisone in DMSO at 10 mg / mL and diluting 10-fold in water.

[0254] For unloaded drug formulations, nS50 and micro-S50 were prepared as above, but without the addition of HCT. A stock of HCT in DMSO at 10 mg / mL was prepared separately and then diluted 10-fold into the preformed nS50 or micro-S50 formulations and vortexed.

[0255] Franz-type diffusion cell (area 1.77 cm 2 The Strat-M® membrane was placed in a 32° C. water bath. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL), and placed in a 32° C. water bath. Hydrocortisone (HCT) formulation (1 mL) was added to the donor chamber. At each time point, 150 μL was removed from the receiver chamber and replaced with an equal amount of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 55% methanol and 45% water, a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 244 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm x 4.6 mm, 3 μm particle size). The cumulative amount of drug permeated per unit time (HCT) for the drug-loaded formulations and the free drug control is shown in FIG.

[0256] The nS50 formulation was micro-S50 (6.88 ± 0.01 μg / cm 2 ), nano-TAG sesame (1.80±0.38μg / cm 2 ), and free drug control (1.29 ± 0.26 μg / cm 2 ) at 7 hours compared with 11.8 ± 0.6 μg / cm 2EMO nanoemulsion provided the best permeation enhancement with a cumulative drug amount of 0.01 mg / kg (Figure 6). These results suggest superior permeation enhancing properties of EMO oil compared to unmodified TAG oil when in emulsion form. Furthermore, EMO nanoemulsion allowed 1.7 times more drug to permeate compared to EMO microemulsion, indicating that the smaller particle size provides better permeation enhancement despite having the same chemical composition.

[0257] Unloaded versions of EMO nano- and microemulsions were also tested. In these formulations, hydrocortisone was added to the preformed nano- and microemulsions. The results in Figure 7 again show that EMO nanoemulsions provide better permeability enhancement compared to EMO microemulsions. However, it was surprising that adding the active ingredient after the formation of the emulsion still improved permeability with minimal differences seen between the loaded and unloaded versions.

[0258] Blends of oat EMO and flaxseed FFA oils were also tested to support the use of other oils for drug permeation. Figure 8 shows that all formulations significantly enhanced hydrocortisone permeability across the Strat-M® membrane. Notably, nFx0 (composed of flaxseed FFA) had the greatest drug permeation (30.6 ± 1.9 μg / cm) over 7 hours compared to the other formulations, likely due to its higher FFA content. 2 ). Indeed, formulations with higher FFA content correlated with more drug permeation with a rank order of nFx0>nOa / Fx25>nOa / Fx50>nOa / Fx75. A similar trend was observed when comparing sesame EMO nanoemulsions with different ratios of EMO and FFA (Figure 9). Again, formulations with higher FFA content correlated with more drug permeation with a rank order of nS25>nS50>nS75.

[0259] Collectively, these data support the use of EMO emulsions for topical and transdermal delivery of drugs, with oil type, FFA content, and particle size influencing permeation enhancement.

[0260] Example 13: CBD Formulations Sesame EMO nanoemulsion was prepared from a combination of sesame EMO and FFA oil. Sesame EMO (0.852 g) and sesame FFA oil (0.648 g) were weighed into a 50 mL metal beaker and heated to 60° C. CBD (150 mg) was added to the oil mixture and mixed gently at 60° C. until the CBD was completely dissolved. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 186 ± 2 nm, PDI = 0.204 ± 0.007).

[0261] Example 14: Clarithromycin A formulation Almond EMO nanoemulsions (nAl75, nAl50, nAl25) were prepared from combinations of almond EMO and FFA oils in different ratios. For nAl75, almond EMO (1.667 g) and almond FFA (0.333 g) were weighed into a 50 mL metal beaker and heated to 60° C. Clarithromycin A (20 mg) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 18.0 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 183 ± 2, PDI = 0.214 ± 0.021).

[0262] nAl50 was prepared using the same procedure as above with almond EMO (1.111 g) and almond FFA (0.889 g). The resulting nanoemulsion was analyzed by DLS (Z average = 196 ± 2, PDI = 0.194 ± 0.018).

[0263] nAl25 was prepared using the same procedure as above with almond EMO (0.556 g) and almond FFA (1.444 g). The resulting nanoemulsion was analyzed by DLS (Z average = 258 ± 6, PDI = 0.228 ± 0.033).

[0264] Coconut EMO nanoemulsion (nCo50) was prepared from a combination of coconut EMO and FFA oils. Coconut EMO (1.136 g) and coconut FFA (0.864 g) were weighed into a 50 mL metal beaker and heated to 60° C. Clarithromycin A (20 mg) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 18.0 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 138 ± 2, PDI = 0.241 ± 0.009).

[0265] MCT EMO nanoemulsion (nMCT50) was prepared from a combination of MCT EMO and FFA oils. MCT EMO (1.266 g) and MCT FFA (0.734 g) were weighed into a 50 mL metal beaker and heated to 60° C. Clarithromycin A (20 mg) was added to the oil mixture and mixed gently at 60° C. to form a fine dispersion. A coarse emulsion was prepared by adding 18.0 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. The resulting nanoemulsion was analyzed by DLS (Z average = 182 ± 3, PDI = 0.265 ± 0.025).

[0266] Example 15: In vitro skin permeation study of hydrocortisone using EMO nanoemulsion Franz-type diffusion cell (area 1.77 cm 2) with a Strat-M® membrane (Lot R1BB11781). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32°C water bath. 1 mL of hydrocortisone (HCT) formulation described below was added to the donor chamber. At each time point, 100 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 55% methanol and 45% water, flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 244 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0267] MCT EMO was derived from 55-65% C8, 35-45% C10, and 2% other MCT oils (Viva Naturals). MCT EMO nanoemulsion was prepared from a combination of MCT EMO and FFA oils. MCT EMO (0.901 g) and MCT FFA (0.593 g) were weighed into a 50 mL metal beaker and heated to 60 °C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60 °C) to the oils. The mixture was subjected to a high shear homogenizer for 30 seconds, resulting in a milky coarse emulsion.

[0268] A linseed EMO nanoemulsion was prepared from a combination of linseed EMO and FFA oils. Linseed EMO (0.914 g) and linseed FFA (0.585 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0269] Oat EMO nanoemulsion was prepared from a combination of oat EMO and FFA oil. Oat EMO (0.862 g) and oat FFA (0.638 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0270] Sesame EMO nanoemulsion was prepared from a combination of sesame EMO and FFA oils. Sesame EMO (0.852 g) and sesame FFA (0.648 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0271] Rosehip EMO nanoemulsion was prepared from a combination of Rosehip EMO and FFA oils. Rosehip EMO (0.893 g) and Rosehip FFA (0.607 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oils. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0272] Almond EMO nanoemulsion was prepared from a combination of almond EMO and FFA oils. Almond EMO (0.833 g) and rosehip FFA (0.667 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oils. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0273] Hemp seed EMO nanoemulsion was prepared from a combination of hemp EMO and FFA oil. Hemp EMO (0.824 g) and MCT FFA (0.676 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion.

[0274] A 10 mg / mL stock of HCT in DMSO was prepared separately and then diluted 10-fold into the preformed nanoemulsion formulation and vortexed.

[0275] Free drug controls were prepared by diluting the HCT DMSO stock 10-fold in water and vortexing.

[0276] All EMO nanoemulsions demonstrated significant permeability enhancement compared to the free drug control (HCT control), as shown in Figure 10. Notably, the MCT nanoemulsion provided the best permeation enhancement (166±13ug / cm^2). These data support the use of various EMO oil type nanoemulsions to enhance drug skin permeation.

[0277] Example 16. In vitro skin permeation study of Cerave hydrocortisone cream with and without oat EMO Franz-type diffusion cell (area 1.77 cm 2) with a Strat-M® membrane (Lot R1BB11781). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32°C water bath. 100 mg of Cerave (1 wt% HCT) was added to the donor chamber with or without the addition of 10% oat EMO. At each time point, 100 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 55% methanol and 45% water, flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 244 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0278] As shown in Figure 11, the addition of oat EMO (10% by weight in this particular example) to Cerave hydrocortisone cream improved HCT permeability by 18-fold at 7 hours compared to Cerave cream without oat EMO, supporting the use of adding EMO as an individual component in topical formulations to improve skin permeation of drugs.

[0279] Example 17. In vitro skin permeation study of salicylic acid with and without nanoemulsions of sesame oil EMO and FFA oil (nS50) Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1DB96259) was placed in a 50 mL beaker. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32° C. water bath. A sesame EMO nanoemulsion with 50% FFA (labeled nS50, not 50% EMO) was prepared from a combination of sesame EMO and FFA oil to give 35.5% MAG, 10.2% DAG, and 50% FFA from a 50 / 50 mixture of sesame EMO and sesame FFA oil. Sesame EMO (0.852 g) and sesame FFA oil (0.648 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. Approximately 1 mL of salicylic acid solution (1 mg / mL in PBS, pH 5-6) or salicylic acid nanoemulsion (1 mg / mL in nS50, pH 5-6) was added to the donor chamber. At each time point, 80 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 50% methanol and 50% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 275 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0280] As shown in Figure 12, no salicylic acid permeation was observed from the free drug control. However, the nanoemulsion formulation allowed permeation of up to 8ug / cm^2 of salicylic acid over a 7 hour period. This is a notable finding as skin permeation of salicylic acid is known to decrease when the pH exceeds pH 3. These data support the use of EMO nanoemulsions to improve salicylic acid skin permeation at physiologically relevant pH (e.g., pH 5-6).

[0281] Example 18. Permeability of Salicylic Acid in Acne Products. Commercially available products containing salicylic acid were obtained and included: (1) CHARLOTTE'S WEB CBDMEDIC Acne Treatment Cream (contains 1% salicylic acid), (2) CERAVE Acne Control Gel (contains 2% salicylic acid), (3) CERAVE Body Wash (for rough & bumpy skin), (4) CLEARASIL Stubborn Acne Control + Marks 1 Minute Mask (contains 2% salicylic acid), (5) NEUTROGENA Rapid Clear Acne Relief Spot Gel (contains 2% salicylic acid), (6) CLEARASIL Rapid Rescue Spot Treatment Gel (contains 2% salicylic acid), and (7) CERAVE Psoriasis Moisturizing Cream (contains 2% salicylic acid).

[0282] For the test samples, each product was used as is or supplemented with 10% EMO. Oat EMO was used for all products tested, except for the sesame EMO used in the CHARLOTTE'S WEB CBDMEDIC acne treatment cream product. Test samples were prepared by adding EMO to the cream product and mixing manually. For example, 100 mg of EMO was added to 900 mg of product and mixed to obtain a test sample containing 10% EMO.

[0283] Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 32°C water bath. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL), and placed in a 32°C water bath. Approximately 100 mg of salicylic acid cream (Neutrogena Rapid Clear and Cerave Psoriasis) with or without 10% oat EMO was added to the donor chamber. At each time point, 80 μL was removed from the receiver chamber and replaced with an equal amount of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 50% methanol and 50% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 275 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0284] Cumulative salicylic acid permeation over time is shown in Figures 12A-12G. As shown, the addition of EMO to these products resulted in mixed results. For example, the addition of 10% sesame EMO did not show significant improvement in the CHARLOTTE'S WEB CBDMEDIC product (Figure 13A), which may be attributed to a matrix effect, without being bound by theory. The addition of EMO to CERAVE Acne Control Gel, CERAVE Body Wash, and CLEARASIL Stubborn Acne Control + Marks 1 Minute Mask reduced the thickening and aggregation of these products upon the addition of EMO compared to the unmodified product (Figures 13B-13D), which may be attributed to matrix and / or compatibility issues, without being bound by theory. Without being bound by theory, it is expected that using a different type of EMO or adding EMO during the manufacturing process, rather than mixing it after the commercial formulation is manufactured, may improve efficacy.

[0285] The addition of EMO to NEUTROGENA Rapid Rescue Spot Treatment Gel and CLEARASIL Rapid Rescue Spot Treatment Gel improved salicylic acid permeability by approximately 2-fold at the earliest time point (1 hour), but the permeation profiles nearly overlapped over 2 hours (Figures 13E-13F). The most substantial difference was observed with EMO added to CERAVE Psoriasis Moisturizing Cream, where a 4-5-fold improvement in salicylic acid permeation was observed over 7 hours (4-fold at 2 and 7 hours) (Figure 13G).

[0286] Example 19. Enhanced permeation of EMO vs. EMO nanoemulsion in cream products. CERAVE Psoriasis Moisturizing Cream containing 2% salicylic acid was prepared with 50% water (control), 50% nOa / Fx-50 (5% total oil component, nanoemulsion, nOa / Fx-50 was prepared as a 10% nanoemulsion in water and diluted to 5%), or 45% water and 5% Oa / Fx-50 (5% total EMO component, non-nanoemulsion). Oat EMO (Oa) and flaxseed FFA oil (Fx) were obtained as disclosed in International Patent Application No. PCT / US2018 / 055583, filed October 12, 2018, published as WO2019 / 075307 and PCT / US2020 / 014182, filed January 17, 2020, WO2020 / 150661, and U.S. Patent Application Publication No. 2020 / 0146307 (U.S. Ser. No. 16 / 746,700), each of which is incorporated herein by reference in its entirety.

[0287] To prepare the nanoemulsions, 0.750 g of each oil (EMO and FFA oil) was added to a 50 mL metal beaker and heated to 60° C. Coarse emulsions were prepared by adding 13.5 mL of water (preheated to 60° C.) to the oils. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was processed at 90% power for two cycles (5 minutes sonication / 2 minutes cooling) to obtain the nanoemulsions. Non-nanoemulsions were prepared by adding 4.5 mL of water to 5 g of product cream and homogenizing, followed by the addition of 2.5 g of oat EMO and 0.25 g of flaxseed FFA oil, followed by homogenization.

[0288] Permeability was measured using standard methods previously described. Franz diffusion cells (area 1.77 cm 2 ) was fitted with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 ml) and placed in a 32° C. water bath.

[0289] As shown in Figure 14, both the addition of nanoemulsion and EMO / FFA oil (non-nanoemulsion) significantly improved the permeability of salicylic acid to a similar extent compared to the control (no added EMO / FFA oil). Without being bound by theory, it is expected that this may be due to the fact that whether the EMO / FFA oil mixture is pre-homogenized before or after it is added to the cream, the components of the EMO / FFA oil mixture are ultimately homogenized with the other lipid components of the cream in the discontinuous phase, resulting in a similar final product whether the EMO / FFA oil mixture was in nanoemulsion or non-nanoemulsion form before it was added.

[0290] Example 20. Permeability of bupivacaine HCl with or without nanoemulsion of sesame oil EMO (nS100). Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 50 mL microcentrifuge tube. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32°C water bath. Sesame EMO nanoemulsion (nS100) was prepared from sesame oil EMO. Sesame EMO (1.50 g) was weighed into a 50 mL metal beaker and heated to 60°C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60°C) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a 1 / 2 inch probe. The emulsion was treated for 2 cycles (5 min sonication / 2 min cool) at 90% power. Approximately 1 mL of bupivacaine solution (0.5 mg / mL in water) or bupivacaine nanoemulsion (0.5 mg / mL in nS100) was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 75% methanol and 25% 10 mM sodium phosphate buffer (pH 7.8), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 263 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm x 4.6 mm, 3 μm particle size).

[0291] As shown in Figure 15, sesame EMO nanoemulsion significantly enhanced the skin permeation of bupivacaine compared to the free drug control. The nanoemulsion allowed for faster permeation (0.45ug / cm^2 at 3 hours compared to undetectable permeation from the free drug control) and overall greater permeation (7-fold improvement at 7 hours). These data support the use of EMO nanoemulsion to improve the skin permeation of basic drugs such as bupivacaine.

[0292] Example 21. Lidocaine Permeability. Franz-type diffusion cell (area 1.77 cm 2 ) with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL), and placed in a 32°C water bath. Approximately 100 mg of ASPERCREME was added to the donor chamber with or without the addition of 5% sesame EMO, 10% sesame EMO, or 10% oat EMO. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal amount of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 70% methanol and 30% 10 mM sodium phosphate buffer (pH 7.8), flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 263 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0293] As shown in Figure 16A, the addition of 10% oat EMO or 10% sesame EMO resulted in significantly faster permeation (36ug / cm^2 at 1 hr) compared to ASPERCREME (7.8ug / cm^2 at 1 hr). There was no difference in the permeation enhancement of 10% oat EMO and 10% sesame EMO. Interestingly, the addition of 5% sesame EMO resulted in a similar overall permeation compared to 10% sesame EMO, which was 3 times better than ASPERCREME alone. Samples were prepared with 2% or 1% sesame EMO and subjected to the same experimental procedure, and the results are shown in Figure 16B. This shows that 5% and 10% sesame EMO significantly enhanced permeation, but 1% and 2% sesame EMO did not enhance permeation to the same extent.

[0294] The lidocaine carbomer formulation was prepared by dissolving lidocaine free base in ethanol and cetyl alcohol and adding it to a 0.4% Carbomer 934p solution, followed by dilution in water and vortexing. The formulation contained ethanol (15%), Carbomer 934p (0.4%), cetyl alcohol (1%), lidocaine (3.5%, equivalent to 4% lidocaine HCl), and water.

[0295] Lidocaine carbomer formulations with sesame EMO were prepared by dissolving lidocaine in ethanol, cetyl alcohol, and sesame EMO and adding it to a 0.4% carbomer 934p solution, followed by dilution in water and vortexing. The formulations contained ethanol (15%), carbomer 934p (0.4%), cetyl alcohol (1%), lidocaine (equivalent to 0.875%, 1.75%, or 3.5%, 1, 2, and 4% lidocaine HCl), sesame EMO (10%), and water.

[0296] Franz-type diffusion cell (area 1.77 cm 2) with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32°C water bath. Approximately 100 mg of formulation was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 70% methanol and 30% 10 mM sodium phosphate buffer (pH 7.8), flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 263 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0297] As shown in Figure 16C, a common in-house carbomer formulation achieved a 2-fold improvement in lidocaine permeation compared to ASPERCREME, even though both had the same concentration of lidocaine. Notably, the addition of 10% sesame EMO to the carbomer formulation significantly improved lidocaine permeation, with a 3.8-fold improvement over the carbomer formulation and an 8-fold improvement over ASPERCREME.

[0298] To determine the effect of drug concentration on permeation performance, formulas containing 1% and 2% lidocaine were made and their permeability was compared to a 4% lidocaine formula and ASPERCREME (Figure 16D). A positive correlation was observed between drug concentration and overall drug permeability. Overall, 10% sesame EMO and a common carbomer lidocaine formulation containing 50-75% drug reduction were comparable to ASPERCREME. At early time points (up to 2 hours), the 2% lidocaine formulation is consistent with ASPERCREME. At later time points (2-5 hours), the 1% lidocaine formulation is consistent with ASPERCREME. Thus, the addition of EMO may be used to reduce drug doses and possibly reduce toxicity while maintaining drug exposure at therapeutic concentrations.

[0299] These data support the use of adding EMO as an individual component to topical formulations to improve the skin permeation of basic drugs such as lidocaine.

[0300] Example 22. In vitro skin permeation study of EMLA (prilocaine and lidocaine) cream with and without sesame EMO. Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 32°C water bath. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL), and placed in a 32°C water bath. Approximately 100 mg of EMLA was added to the donor chamber with or without the addition of 0.5, 1, 2.5, 5, and 10% sesame EMO. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 70% methanol and 30% 10 mM sodium phosphate buffer (pH 7.8), flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 263 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0301] As shown in Figures 17A-17B, the addition of sesame EMO to the EMLA cream improved the permeation of both lidocaine and prilocaine in all cases. The addition of 0.5% EMO increased the permeation rates of prilocaine and lidocaine by more than three-fold compared to EMLA cream without EMO. The addition of >0.5% sesame EMO increased prilocaine and lidocaine by more than four-fold. These data support the use of adding EMO as an individual component to topical formulations to improve the skin permeation of drugs such as lidocaine and prilocaine.

[0302] Example 23. In vitro permeation study of Voltaren Diclofenac Cream with and without Sesame EMO. Franz-type diffusion cell (area 1.77 cm 2) with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32°C water bath. 100 mg of Voltaren was added to the donor chamber with or without the addition of 10% sesame EMO. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 70% methanol and 30% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 280 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0303] As shown in Figure 18, the addition of sesame EMO (10% by weight in this particular example) to VOLTAREN diclofenac cream improved diclofenac permeation by 1.5-fold at 5 hours compared to Voltaren cream without sesame EMO. The addition of EMO also accelerated permeation as evidenced by the 6-fold improvement in permeation at the earliest time point (0.5 hours). These data support the use of adding EMO as an individual component to topical formulations to improve the skin permeation of drugs such as VOLTAREN.

[0304] Example 24. In vitro skin permeation study of cannabadiol (CBD) cream with or without EMO. Franz-type diffusion cell (area 1.77 cm 2) was fitted with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with 0.5% brij98 solution (10 mL), and placed in a 32°C water bath. 100 mg of GARDEN OF LIFE CBD Intensive Recovery Cream was added to the donor chamber with or without the addition of 10% sesame EMO, 10% coconut EMO, or 10% sunflower EMO. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh 0.5% brij98 solution to maintain constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 75% methanol and 25% water, flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 275 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0305] As shown in Figure 19, the CBD cream showed no CBD permeation over a 5 hour period. However, the addition of 10% coconut or sunflower EMO achieved 1.4ug / cm^2 CBD permeation, and the addition of 10% sesame EMO achieved 2.0ug / cm^2 CBD permeation over a 5 hour period. These data support the use of adding EMO as an individual ingredient to topical formulations to improve the skin permeation of hydrophobic drugs such as CBD.

[0306] Example 25. In vitro skin permeation study of resveratrol cream with and without sesame EMO. Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 32°C water bath. The receptor chamber was fitted with a stir bar, filled with 0.5% brij98 solution (10 mL), and placed in a 32°C water bath. Approximately 100 mg of SkinCeuticals Resveratrol BE Cream with or without the addition of 10% Sesame EMO was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh 0.5% brij98 solution to maintain constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 45% methanol and 55% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 303 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0307] As shown in Figure 20, the addition of 10% sesame EMO achieved a 4-fold and 5-fold increase in resveratrol permeation at 8 and 24 hours, respectively, compared to the cream alone. These data support the use of adding EMO as an individual component to topical formulations to improve skin permeation of hydrophobic drugs such as resveratrol.

[0308] Example 26. In vitro skin permeation study of retinyl palmitate cream with and without EMO. Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 32°C water bath. The receptor chamber was fitted with a stir bar, filled with 0.5% brij98 solution (10 mL), and placed in a 32°C water bath. Approximately 100 mg of cream (Revitalift Anti-Wrinkle Eye Cream, Revitalift Anti-Wrinkle Moisturizer, Revitalift Cica Cream) with or without the addition of 10% sesame EMO was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal amount of fresh 0.5% brij98 solution to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 98% methanol and 2% water, flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 325 nm. The column used was an Ascentis® Express C8 column (150 mm×4.6 mm, 2.7 μm particle size).

[0309] As shown in Figures 21A-21C, no permeation of retinyl palmitate was observed from any of the three products tested. However, the addition of 10% sesame EMO enabled permeation of superhydrophobic retinyl palmitate in all three products, reaching nearly 9ug / cm^2 after 24 hours. These data support the use of adding EMO as an individual component to topical formulations to improve skin permeation of hydrophobic drugs such as retinyl palmitate.

[0310] Example 27. In vitro skin permeation study of retinol cream with and without EMO. Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 32°C water bath. The receptor chamber was fitted with a stir bar, filled with 0.5% brij98 solution (10 mL), and placed in a 32°C water bath. Approximately 100 mg of cream (Neutrogena Ageless Intensive Anti-Wrinkle, and Neutrogena Healthy Skin Anti-Wrinkle Night) with or without the addition of 10% Sesame EMO was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal amount of fresh 0.5% brij98 solution to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 90% methanol and 10% water, flow rate of 1.000 mL / min, column temperature of 40° C., and detection at 325 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0311] As shown in Figures 22A-22B, the addition of Sesame EMO improved retinol permeability by 8-fold and 2-fold at 6 and 24 hours, respectively, compared to the Ageless Intensive product alone. For the Healthy Skin product, the addition of EMO improved retinol permeation by 9-fold at 7 and 24 hours. This supports the use of adding EMO as an individual ingredient in topical formulations to improve skin permeation of hydrophobic vitamins such as retinol.

[0312] Example 28. In vitro skin permeation study of trifluoroacetyl tripeptide-2 with and without sesame oil EMO and FFA oil nanoemulsions. Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 50 mL microcentrifuge. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32° C. water bath. Sesame EMO nanoemulsion (nS50) was prepared from a combination of sesame EMO and FFA oils. Sesame EMO (0.852 g) and sesame FFA (0.648 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. Approximately 1 mL of trifluoroacetyl tripeptide-2 (Cayman Chemical Company) solution (10 mg / mL in 10% DMSO in water) or trifluoroacetyl tripeptide-2 nanoemulsion (10 mg / mL in 10% DMSO in nS50) was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 55% methanol and 45% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 210 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm x 4.6 mm, 3 μm particle size).

[0313] As shown in Figure 23, no peptide permeation was observed from the free peptide control at 6 hours and only 1.1ug / cm^2 was observed after 24 hours. However, the nanoemulsion formulation significantly accelerated permeation as evidenced by detectable peptide permeation at the earliest time point (1 hour). The nanoemulsion formulation also significantly improved overall skin permeation, achieving a notable 38-fold improvement in peptide permeation over 24 hours. These data support the use of EMO nanoemulsions to improve peptide skin permeation.

[0314] Example 29. In vitro skin permeation study of hexapeptide-11 with and without nanoemulsions of sesame oil EMO and FFA oil (nS50). Franz-type diffusion cell (area 1.77 cm 2A Strat-M® membrane (Lot R1KB43611) was placed in a 50 mL microcentrifuge. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32° C. water bath. Sesame EMO nanoemulsion (nS50) was prepared from a combination of sesame EMO and FFA oils. Sesame EMO (0.852 g) and sesame FFA (0.648 g) were weighed into a 50 mL metal beaker and heated to 60° C. A coarse emulsion was prepared by adding 13.5 mL of water (preheated to 60° C.) to the oil. The mixture was subjected to a high shear homogenizer for 30 seconds to obtain a milky coarse emulsion. The coarse emulsion was then transferred to a QSonica Q700CA sonicator equipped with a ½ inch probe. The emulsion was treated for two cycles (5 min sonication / 2 min cool) at 90% power. Approximately 1 mL of hexapeptide-11 (active peptide) solution (10 mg / mL in 10% DMSO in water) or hexapeptide-11 nanoemulsion (10 mg / mL in 10% DMSO in nS50) was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 60% methanol and 40% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 210 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm x 4.6 mm, 3 μm particle size).

[0315] As shown in Figure 24, no peptide permeation was observed over 24 hours from the free peptide control. However, the nanoemulsion formulation significantly enhanced overall skin permeation, achieving a remarkable 111ug / cm^2 over 24 hours. These data support the use of EMO nanoemulsion to improve peptide skin permeation.

[0316] Example 30. In vitro skin permeation study of 5-fluorouracil (5-FU) cream with or without sesame EMO. Franz-type diffusion cell (area 1.77 cm 2 ) with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL), and placed in a 32°C water bath. Approximately 100 mg of formulated 5-FU cream (5% 5-FU, Mayne Pharma) with or without the addition of 10% sesame EMO was added to the donor chamber. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS solution to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 4% methanol and 96% phosphoric acid (0.1%), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 265 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0317] As shown in Figure 25, the addition of 10% sesame EMO achieved a 13-fold and 8-fold increase in 5-FU permeation at 3 and 24 hours, respectively, compared to the cream alone. These data support the use of adding EMO as an individual component in topical formulations to improve skin permeation of chemotherapy agents such as 5-FU.

[0318] Example 31. Analysis of non-oil components in enzyme modified oils. For LC / MS / MS analysis, canola oil or canola EMO samples were derivatized with 3-picolylamide. Analysis was performed using positive ionization mode for total fatty acids and lipodomics and negative ionization for lipodomics. Thermo Scientific Freestyle & LipidSearch were used for analysis, with Orbitrap fusion methodology including data-dependent acquisition MS (total fatty acids) & MS. Non-oil components were generally preserved or enriched, as shown in Figure 26. Coenzymes were also found to be enriched.

[0319] Example 32. In vitro skin permeation study of ASPERCREME (lidocaine) containing EMO, EMO / FFA oil, FFA oil, or TAG oil Franz-type diffusion cell (area 1.77 cm 2 A Strat-M® membrane (Lot R1KB43611) was placed in the receptor chamber. The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32° C. water bath. Approximately 100 mg of Aspercreme was added to the following: 10% sesame EMO 50% Sesame EMO 10% mixture of sesame FFA oil (total FFA 50%) (S50) 10% sesame FFA oil 10% Sesame Oil (Triglycerides, TAG) The donor chamber was added with or without PBS. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 70% methanol and 30% 10 mM sodium phosphate buffer (pH 7.8), a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 263 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0320] FIG. 27 shows the cumulative permeated lidocaine over a 5 hour period.

[0321] Only the addition of sesame EMO significantly enhanced the permeability of lidocaine compared to the Aspercreme product. The addition of sesame TAG oil did not substantially affect the permeability of lidocaine. Surprisingly, the addition of a mixture of sesame EMO / FFA or sesame FFA significantly decreased the permeability of lidocaine.

[0322] Example 33. In vitro skin permeation study of CERAVE hydrocortisone cream containing EMO, EMO / FFA oil, FFA oil, or TAG oil. Franz-type diffusion cell (area 1.77 cm 2 ) was fitted with a Strat-M® membrane (Lot R1KB43611). The receptor chamber was fitted with a stir bar, filled with PBS (10 mL) and placed in a 32° C. water bath. Approximately 100 mg of Cerave hydrocortisone cream was added to the following: 10% sesame EMO 50% sesame EMO and 10% sesame FFA oil mixture (total FFA 50%) (S50) 10% sesame FFA oil 10% Sesame Oil (Triglycerides, TAG) The donor chamber was added with or without PBS. At each time point, 70 μL was removed from the receiver chamber and replaced with an equal volume of fresh PBS to maintain a constant volume. Aliquots from each time point were analyzed by HPLC to determine the amount of drug permeating the membrane over time. The HPLC system consisted of an LC-20AD pump, a SIL-20AC HT autosampler, a CTO-20A column oven, and an SPD-20A UV / vis detector (Shimadzu Scientific Instruments, Inc.). The HPLC conditions were: injection volume of 30 μL, isocratic elution with a mobile phase consisting of 55% methanol and 45% water, a flow rate of 1.000 mL / min, a column temperature of 40° C., and detection at 244 nm. The column used was a SUPELCOSIL LC-18-T column (150 mm×4.6 mm, 3 μm particle size).

[0323] FIG. 28 shows the cumulative permeation of hydrocortisone over a 5 hour period.

[0324] The addition of either sesame EMO or a mixture of sesame EMO and sesame FFA provided the greatest improvement in hydrocortisone permeation. The addition of FFA also provided only a significant increase in permeability. The addition of sesame TAG oil provided only a slight improvement compared to the cream product.

[0325] The foregoing description of specific embodiments of the present disclosure has been presented for purposes of illustration and description. The exemplary embodiments have been chosen and described to best explain the principles of the present disclosure and its practical application, thereby enabling those skilled in the art to best utilize the subject matter, and various embodiments with various modifications are suitable for the particular uses contemplated. Different features and disclosures of the various embodiments within the present disclosure may be combined within the scope of the present disclosure.

Claims

1. 1. A composition comprising an oil dispersed in a liquid, the oil being in the form of droplets or particles, the oil comprising free fatty acids (FFAs) in an amount of at least 5% by weight of the total weight of the oil, the free fatty acids comprising two or more different fatty acids, the oil being substantially free of triacylglycerols (TAGs), and the droplets or particles having a Z-average size of about 300 nm or less as measured by dynamic light scattering (DLS).

2. 2. The composition of claim 1, wherein the composition does not contain any exogenous additives having surfactant and / or emulsifier properties that are not naturally present in the oil in an amount sufficient to enhance droplet stability.

3. 2. The composition of claim 1, wherein the composition does not contain any exogenous additives having thickening or crystallization inhibiting properties not naturally occurring in the oil in an amount sufficient to thicken the composition or inhibit crystallization formation, respectively.

4. The composition of claim 1 , wherein the droplets or particles have an average zeta potential of less than −30 mV.

5. 10. The composition of claim 1, wherein the droplets or particles have a polydispersity index (PDI) of less than 0.

3.

6. 10. The composition of claim 1, wherein the Z-average size of the droplets or particles does not change by more than 15% over a period of 28 days when stored at room temperature.

7. The composition according to any one of claims 1 to 6, further comprising an active ingredient.

8. 1. An oil composition comprising: Monoacylglycerol (MAG) in an amount of about 10% to about 80% by weight of the total weight of the oil; Free fatty acids (FFA) in an amount of about 20% to about 90% by weight of the total weight of the oil. Including, The FFA comprises two or more different fatty acids, and the oil is substantially free of triacylglycerols (TAGs); oil composition.

9. 9. The composition of claim 8, wherein the oil is derived from MCT oil and the two or more different fatty acids comprise C8:0 in an amount from about 50% to about 65% of the total fatty acid content of the oil, and C10 in an amount from about 35% to about 50% of the total fatty acid content of the oil.

10. 9. The composition of claim 8, wherein the oil is derived from canola oil and the two or more different fatty acids comprise C18:1 in an amount from about 55% to about 70% of the total fatty acid content, and C18:2 in an amount from about 15% to about 30% of the total fatty acid content.

11. The composition according to any one of claims 8 to 10, further comprising an active ingredient.

12. 12. The composition of claim 11, wherein the active ingredient is selected from the group consisting of steroids, nonsteroids, analgesics, plant extracts, antioxidants, and vitamins or dietary supplements.

13. 12. The composition of claim 11, wherein the active ingredient is an analgesic selected from the group consisting of bupivacaine, lidocaine, prilocaine, and combinations thereof.

14. A composition comprising a first component and a second component, wherein the first component is selected from the group consisting of a cream, a lotion, a body wash, or a lubricant, and the second component is an additive comprising the composition of any one of claims 1 to 6 or 8 to 10.

15. The composition of claim 14, further comprising a third component, the third component being an active ingredient selected from the group consisting of a steroid drug, a non-steroid drug, an analgesic drug, a plant extract, an antioxidant, and a vitamin or nutritional supplement.

16. The first component is a cream, the third component is a steroid drug, the steroid is hydrocortisone, and the hydrocortisone is at least 6 μg / cm per 7 hours. ２ The composition of claim 15, having a skin permeability of 17. The composition of claim 15, wherein the first component is a lubricant, the third component is an analgesic, and the analgesic is selected from the group consisting of bupivacaine, lidocaine, prilocaine, and combinations thereof.

18. The composition of claim 15, wherein the analgesic has a skin permeability of at least 6 μg / cm 2 per 7 hours.

19. The composition of claim 15, wherein the first component is a body wash.

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