Phytosome-based delivery system for bioactive ingredients, method for obtaining thereof and compositions comprising thereof

Abstract

The present invention discloses a phytosome-based delivery system for bioactive ingredients, as well as the method for obtaining thereof and compositions comprising thereof. More specifically, the present invention relates to phytosomes for an eco-friendly and safe delivery of bioactive compounds, especially natural occurring bioactive compounds, wherein the phytosomes are obtained by a green and eco-friendly method and are useful in the pharmaceutical, cosmetic and foodstuff area.

Description

PHYTOSOME-BASED DELIVERY SYSTEM FOR BIOACTIVE INGREDIENTS, METHOD FOR OBTAINING THEREOF AND COMPOSITIONS COMPRISING THEREOF

[0001] The present application claims the benefit of priority to the Portuguese provisional patent application no. 118881, filed August 22, 2023, the contents of which is incorporated herein by reference.

[0002] The present invention is encompassed in the pharmaceutical sciences field and discloses a phytosome-based delivery system for bioactive ingredients, as well as the method for obtaining thereof and compositions comprising thereof.

[0003] The phytosomes are an eco-friendly and safe system for the delivery of bioactive compounds, especially natural occurring bioactive compounds. They are obtained by a green and eco-friendly method and are useful in the pharmaceutical, cosmetic and foodstuff area.

[0004] Natural sources, mainly plant extracts, present a great deal of biological properties and could be valuable sources of bioactive ingredients for human health. However, the hydrophilic properties of some relevant compounds found in those extracts have always been a challenge in formulation development posed by the difficulties encountered in finding appropriate delivery systems.

[0005] Polyphenols are the most popular phytochemicals with high solubility in water (they are hydrophilic due to their high number of hydroxyl groups) and present low solubility in lipid phases. Thus, low absorption / permeation of these valuable bioactive compounds considerably impairs their transport through a biological cell membrane (which contains 90 % of phospholipids).

[0006] Besides, factors such as high structural sensitivities, poor bioavailability, high intrasubject / intersubject variability, and lack of dose proportionality limit their exploitation in innovative products and thus their wider consumption1, 2.

[0007] The lack of cell-like carriers before the 80’s led researchers to the development of a potent carrier to deliver both hydrophilic and lipophilic bioactives, and, at the same time, solve the challenges of delivering hydrophilic bioactive compounds1.

[0008] Phytosomes, which are phospholipid-based vesicles, were developed in the late 80’s by Indena company (Milan, Italy). They are cell-like carriers composed of phospholipid bilayers, in which plant extracts (which commonly have lipophilic and hydrophilic bioactives) are loaded to increase the rate of absorption / permeation, also improving bioavailability, and enhancing protection of bioactives1, 3.

[0009] Even though there is a variety of micro / nanocarriers used in the delivery of bioactives, phytosomes are recognized as biocompatible and eco-friendly carriers and are science / market approved.

[0010] Phytosomes opened a new perspective in science and technology development that has been exploited for a range of applications, namely, therapeutic, food, and health / body care industries. They rapidly became widely used carriers to deliver plant extracts and their bioactives and successfully found their place in the global market. Nowadays, worldwide, several famous companies use phytosome technology directly or indirectly in their products, showing their fundamental health benefits and with a high commercial impact.

[0011] Phytosomes are prepared by hydrogen binding between the choline site of phospholipids and the polar site of bioactive compounds which is defined by specific ratios of 0.5:1, 1:1, 1:2, and 1:31,4,5. Nevertheless, phytosomes still raise significant health concerns due to the pattern of their preparation methods. In fact, organic solvents are used in one of the critical steps of phytosome formation1,5.

[0012] In view of this context, the present invention herein proposes a new and inventive phytosome-based delivery system for bioactive ingredients (e.g., phytoconstituents, nutraceuticals, cosmeceuticals, and / or natural-based drugs), as well as the method for obtaining thereof and compositions comprising thereof.

[0013] More specifically, the present invention relates to phytosomes for an eco-friendly and safe delivery of bioactive compounds, especially natural occurring bioactive compounds, wherein the phytosomes are obtained by a green and eco-friendly method and are useful in the pharmaceutical, cosmetic and foodstuff area.

[0014] In a first aspect, the present invention discloses a phytosome-based delivery system comprising:

[0015] - physiologically compatible lipids selected from the group consisting of phosphoglycerides;

[0016] - biocompatible and biodegradable lipids selected from the group consisting of glycerides and alcohol-based lipids; and

[0017] - active ingredients selected from the group consisting of plant extracts and phytochemicals;

[0018] wherein the mass ratio between the physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:20; and

[0019] wherein the mass ratio between the active ingredients and the physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:50.

[0020] In a second aspect, the present invention discloses a method for obtaining the phytosome-based delivery system comprising the steps of:

[0021] a. dissolving the bioactive ingredient in ethanol or ethanolic aqueous solution;

[0022] b. dissolving the physiologically compatible lipids in biocompatible and biodegradable lipids;

[0023] c. mixing the solutions obtained from steps (a) and (b); and

[0024] d. removing the excess of solvent;

[0025] e. hydrating the phytosome obtained in step (d); and

[0026] f. drying the hydrated phytosome obtained in step (e);

[0027] wherein steps (a) and (b) can be performed in any order.

[0028] In a third aspect, the present invention discloses a composition comprising the phytosome-based delivery system in the form of powders, capsules, granules, pellets, tablets, creams, gels, ointments, pastes, suspensions, lotions, or syrups, wherein the mentioned composition is for topical or oral use as a pharmaceutical, cosmetic or food product.

[0029] Based on literature knowledge and Indena patent, phytosomes get shaped by dissolving lipids in an aprotic solvent (methylene chloride, dioxane, acetone, or methyl acetate) and mixing it with the bioactive compounds of interest dissolved in protic solvents (methanol and ethanol)1.

[0030] The present invention focuses on eliminating the need of organic solvents of high toxicological risk and subsequently eliminating the traces of solvents that remain in the final product by proposing a new and inventive method for obtaining the phytosome-based delivery system claimed.

[0031] In the present invention, phytosomes are obtained by dissolving selected physiological lipids in glycerol whereas bioactives are dissolved in ethanol. Both solutions are then mixed for self-assembling the lipids into vesicles loaded with bioactives and ethanol is then removed.

[0032] Thus, there is no use of toxic organic solvents for dissolving the physiological lipids used as a carrier. That measure will considerably increase the physiological character of the delivery system obtained and diminish the risk of adverse effects from the presence of organic solvents that can reach lungs and other organs of the reticuloendothelial system, thereby boosting hepatoprotective properties.

[0033] The phytosome-based delivery system proposed in the present invention presents a dual function: it is a physiological, green, eco-friendly system able to carry both lipophilic and hydrophilic bioactive ingredients.

[0034] It comprises biocompatible and biodegradable lipids selected from the group consisting of glycerides and alcohol-based lipids, therefore being able to include a series of phospholipids that contain a polar side as a headgroup and a non-polar side as tail (e.g. phosphatidylcholine and phosphatidylserine).

[0035] Due to its structure, phosphatidylserine can pass through the human brain barrier (BBB), being an ideal carrier for the delivery of bioactive ingredients to the central nervous system (CNS) for the treatment of brain disorders.

[0036] Also, the phytosome-based delivery systems obtained can be developed into solid (powders, capsules, granules, pellets, tablets), semi-solid (creams, gels, ointments, pastes) and liquid (suspensions, lotions, syrups) compositions, being applicable for use in pharmaceutical, cosmetic and foodstuff products.

[0037] In order to facilitate an understanding of the principles according to the embodiments of this invention, reference will be made to the illustrated embodiments in the Figures and the language used to describe them.

[0038] It should also be understood that there is no intention to limit the scope of the invention to the content of the Figures and that modifications to the inventive features illustrated herein, as well as additional applications of the illustrated principles and embodiments, which would normally occur to a person skilled in the art having possession of this description, are considered within the scope of the claimed invention.Fig.1

[0039] represents the method for obtaining the phytosome-based delivery system of the present invention.Fig.2

[0040] is the Fourier transformed infra-red spectroscopy (FTIR) spectra showing the occurrence of hydrogen binding between functional groups of the bioactive ingredient and the phosphatidylcholine.Fig.3

[0041] are SEM images of the phytosome-based delivery system of the present invention.Fig.4

[0042] graphically represents (A) zeta potential and (B) mean particle size of the phytosome-based delivery system of the present invention, obtained upon hydration with pectin-based solution.Fig.5

[0043] graphically represents (A) zeta potential and (B) mean particle size of the phytosome-based delivery system of the present invention, obtained upon hydration with chitosan-based solution.Fig.6

[0044] graphically represents the release study of the phytosome-based delivery system of the present invention coated with a negatively charged natural polymer (dried powder obtained by spray dryer).Fig.7

[0045] graphically represents the rheology analysis of hydrogel composition comprising the phytosome-based delivery system of the present invention stored at 4 ºC for seven days.

[0046] In a first aspect, the present invention discloses a phytosome-based delivery system comprising:

[0047] – physiologically compatible lipids selected from the group consisting of phosphoglycerides;

[0048] – biocompatible and biodegradable lipids selected from the group consisting of glycerides and alcohol-based lipids; and

[0049] – active ingredients selected from the group consisting of plant extracts and phytochemicals;

[0050] wherein the mass ratio between the physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:20; and

[0051] wherein the mass ratio between the active ingredients and the mixture of physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:50.

[0052] In a preferred embodiment of the present invention, the phosphoglycerides are selected from the group consisting of phosphatidylcholine, phosphatidylserine, and mixtures thereof.

[0053] In a preferred embodiment of the present invention, the glycerides are selected from the group consisting of triglycerides based on medium and long-chain fatty acids and sterols.

[0054] Medium-chain triglycerides are selected from the group consisting of caprylic triglyceride, capric triglyceride, lauric triglyceride, and mixtures thereof, while long-chain triglycerides are selected from the group consisting of palmitic triglyceride, stearic triglyceride, oleic triglyceride, linoleic triglyceride, arachidonic triglyceride, eicosapentaenoic triglyceride, docosahexaenoic triglyceride, and mixtures thereof.

[0055] Sterols are selected from the group consisting of cholesterol, ergosterol, phytosterols, stigmasterol, campesterol, beta-sitosterol, sitostanol, brassicasterol, and mixtures thereof.

[0056] In a preferred embodiment of the present invention, the alcohol-based lipids are selected from the group consisting of glycerol, propylene glycol and mixtures thereof.

[0057] In a preferred embodiment of the present invention, the plant extracts are selected from the group consisting of coffee, silverskin, pomegranate peels, grape pomace, olive pomace,Arnica chamissonisand Cumin extracts.

[0058] In a preferred embodiment of the present invention, the phytochemicals are selected from the group consisting of phenolic, flavonoids, alkaloids, anthocyanins, fibers, vitamins, and fatty acids. Since phytochemicals are phytonutrients, phytoconstituents and bioactive compounds found in the plant extracts, they might differ based on the plant extract type.

[0059] In a second aspect and as shown in, the present invention discloses a method for obtaining the phytosome-based delivery system comprising the steps of:

[0060] a. dissolving the bioactive ingredient in ethanol or ethanolic aqueous solution;

[0061] b. dissolving the physiologically compatible lipids in biocompatible and biodegradable lipids;

[0062] c. mixing the solutions obtained from steps (a) and (b);

[0063] d. removing the excess of solvent;

[0064] e. hydrating the phytosome obtained in step (d); and

[0065] f. drying the hydrated phytosome obtained in step (e);

[0066] wherein steps (a) and (b) can be performed in any order.

[0067] In step (a), the amount of ethanol or ethanolic aqueous solution and the temperature will vary depending on the bioactive ingredient to be loaded. In preferred embodiments of the present invention, the ethanol is absolute ethanol and the mass ratio between the bioactive ingredient and the ethanol varies from 1:20 to 1:200.

[0068] In other preferred embodiments of the present invention, the temperature is the same temperature used for extraction / fractionation of the bioactive ingredient, provided that the temperature is not higher than 60 ºC. Preferably, the temperature varies from 0 to 60 ºC, more preferably from 25 to 60 ºC.

[0069] In step (b), the mass ratio between the physiologically compatible lipids and biodegradable lipids varies from 1:1 to 1:20. In preferred embodiments of the present invention, the step occurs at a temperature that varies from 0 to 60 ºC, more preferably from 25 to 60 ºC.

[0070] A slight increase of temperature may be needed for dissolving the lipids. In case that occurs, the solution must be cooled down to the same temperature of the solution obtained in step (a).

[0071] In step (c), the mass ratio between the active ingredients and the mixture of physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:50. In preferred embodiments of the present invention, the step occurs at the same temperature of step (a), i.e., from 0 to 60 ºC, more preferably from 25 to 60 ºC.

[0072] At least one of steps (a), (b) and (c) are performed under stirring, wherein the time spent on each step varies according to the time needed to completely solubilize / mix the components. In preferred embodiments of the present invention, the time varies between 1 and 2 hours.

[0073] In step (d), after removing the excess of solvent, the phytosome obtained is allowed to rest overnight (from 6 to 12 hours).

[0074] In step (e), the phytosomes obtained in step (d) are hydrated by using water or an aqueous solution of either a positively or negatively charged natural polymers for coating. In a preferred embodiment of the present invention, the negatively charged natural polymers are at least one selected from the group consisting of pectin, alginate, starch, Arabic gum, maltodextrin, carboxylated chitosan, xanthan gum, casein, and mixtures thereof. In a preferred embodiment of the present invention, the positively charged natural polymers are at least one selected from the group consisting of zein, chitosan, and mixtures thereof.

[0075] In step (f), the hydrated phytosome obtained in step (e) is subsequently dried by spray-drying or by freeze-drying (lyophilization).

[0076] The phytosomes-based delivery system of the present invention can be developed into solid (powders, capsules, granules, pellets, tablets), semi-solid (creams, gels, ointments, pastes) and liquid (suspensions, lotions, syrups) compositions.

[0077] The dried phytosomes obtained at the end of the method disclosed in the present invention can be used directly in pharmaceutical, cosmetic and also food products formulated as powders, granules, capsules, pellets, tablets (solid formulations).

[0078] To develop phytosomes-based semi-solid and liquid compositions, the dried phytosomes are loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) or nanoemulsions (NE) comprising at least one of the groups consisting of lipids, emulsifiers, and co-emulsifiers. Then, these phytosomes-loaded dispersions can then be formulated as suspensions, creams, gels, ointments, pastes, syrups, lotions, for topical or oral administration.

[0079] The present invention was developed to answer the concerns encountered with the use of delivery systems that may pose humans and the environment at toxicological risks.

[0080] The phytosome-based delivery system of the present invention comprises fully green components and is produced by a fully green method, which is also of low cost, less time-consuming and that can be easily scaled-up.

[0081] The phytosome-based delivery system of the present invention further provides a high-performance carrier to protect bioactive compounds and enhance their permeation through cell membranes for a range of administration routes.Examples

[0082] In order to characterize the phytosome-based delivery system of the present invention, several tests were performed.

[0083] Initially, the physicochemical properties of the phytosome-based delivery system of the present invention were analyzed by Fourier transformed infra-red spectroscopy (FTIR) to determine any potential interaction of bioactive with the lipids composing the vesicles.

[0084] In, the FTIR spectra confirms the interaction between the bioactive ingredient (plant extract) and the phosphatidylcholine before hydration step (sampling from overnight rest in desiccator).

[0085] It is possible to note that the typical functional groups of the materials (bioactive ingredient and phosphatidylcholine) were suppressed when formulated as the phytosome-based delivery system of the present invention. Besides, the overlap of spectral regions, with significant changes in the fingerprint area of these materials, is an additional confirmation of the chemical interactions that occurred between these two components.

[0086] The morphology of the phytosome-based delivery system of the present invention was also analyzed by scanning electron microscopy (SEM). As can be seen in, phytosomes coated with a natural polymer (pectin) is shown as individualized spherical vesicles with a smooth surface and a size around 1 – 5 µm.

[0087] According to the release study, shown on, the developed eco-friendly phytosomes coated with pectin showed a considerable slow-release time with a good fitting to the zero-order kinetics.

[0088] The encapsulation efficiency, loading capacity, release profile, zeta potential, particle size, rheological behavior and texture analysis were also determined as qualitative and quantitative parameters.

[0089] Positively charged phytosomes could be obtained when using positively charged natural polymer (e.g., chitosan) in the hydration step and / or as coating, whereas negatively charged phytosomes could be obtained when using positively charged natural polymer (e.g., pectin) in the hydration step and / or as coating.

[0090] The zeta potential and mean particle size of the phytosome-based delivery system of the present invention obtained upon hydration with pectin-based solution and chitosan-based solution are disclosed in Figs. 4 and 5 and Tables 1-4 below, respectively.

[0091] Table 1 – Zeta potential of the phytosome-based delivery system of the present invention obtained upon hydration with pectin-based solution.RunMobilityZeta Potential (mV)Rel. Residual1- 2.13- 30.040.05582- 1.70- 23.980.03403- 1.36- 19.220.03464- 1.97- 27.690.06945- 1.35- 18.960.05476- 2.06- 28.990.0569Mean- 1.76- 24.810.0509Std. error0.141.990.0057Combined- 1.72- 24.220.0124

[0092] Table 2 – Mean particle size of the phytosome-based delivery system of the present invention obtained upon hydration with pectin-based solution.RunEff. Diam (nm)Half width (nm)Polydispersity1200.855.00.0752197.262.70.1013200.151.60.0664198.256.40.0815198.867.40.1156200.957.80.0837198.264.30.1058197.861.80.0989196.652.90.07210200.456.40.079Mean198.958.60.088Std. Error0.51.60.005Combined199.058.50.086

[0093] Table 3 – Zeta potential of the phytosome-based delivery system of the present invention obtained upon hydration with chitosan-based solution:RunMobilityZeta potential (mV)Rel. residual11.8826.410.028021.6723.570.026631.6523.190.023341.9026.720.028051.8125.530.033162.1229.840.0184Mean1.8435.880.0262Std. error0.070.990.0020Combined1.8325.760.0119

[0094] Table 4 – Mean particle size of the phytosome-based delivery system of the present invention obtained upon hydration with chitosan-based solution:RunEff. Diam (nm)Half width (nm)Polydispersity1140.863.60.2042160.766.30.1703158.070.30.1984156.169.20.1975161.675.30.2176161.975.10.215Mean156.570.00.200Std. error3.31.90.007Combined156.069.50.199

[0095] Results show that the developed phytosomes show a high electrostatic stability, with mean particle size being below 200 nm with a monodispersed size distribution.

[0096] As a proof of concept, one semi-solid composition was developed, namely, a Carbopol-based hydrogel. The qualitative and quantitative composition of the Carbopol-based hydrogel is given in Table 5 below:

[0097] Table 5 – Qualitative and quantitative composition of the Carbopol-based hydrogel comprising the phytosome-based delivery system of the present invention:Ingredient% (m / m)Phytosome-based delivery system1.0Carbopol2.0Triethylenediamine1.0Preservative (e.g., methylparaben, propylparaben)max. 0.1Water add100

[0098] In regards the rheology analysis, incorporating the phytosome-based delivery system of the present invention in a hydrogel provides a good shear and elastic properties with appropriate viscosity (see Table 6 below).

[0099] The Carbopol-based hydrogel composition comprising the phytosome-based delivery system of the present invention was stored at 4 ºC for seven days, and no evidence of two-phase, water loss and abnormal physiochemical properties are observed (see).

[0100] Table 6: Rheology analysis of the Carbopol-based hydrogel comprising the phytosome-based delivery system of the present invention:Frequency (Hz)Viscous modulus (Pa)Elastic modulus (Pa)Shear viscosity (Pa.s)Max95.67563.109.09Median51.74470.6075.35Min34.64417.80667.20Average56.48478.33160.27

[0101] As noted, good physicochemical properties were observed for all the developed products concerning particle size, zeta potential, encapsulation efficiency (> 90 %), loading capacity, short and long-term stability, rheology, and texture analysis.

[0102] The high encapsulation efficiency considerably improved protection of the bioactive ingredients by reducing the risk of their degradation and / or diffusion into the dispersion media.

[0103] The lipids used further stabilize the negative charge of the phytosome-based delivery system, which could compromise the absorption and permeation of the system through biological membranes due to repulsion between the two negative surfaces (phytosome and membrane).

[0104] Due to the use of physiological lipids in their composition, the phytosome-based delivery system disclosed in the present invention promote enhanced absorption of the payloads in the gut, in case intended for oral administration, while provide synergic hepatoprotective effect (due to hepatoprotective activity of phosphatidylcholine) and indirectly protect liver and kidney from detoxifications.

[0105] If intended for topical administration, phytosomes promote skin / mucosal permeation. Therefore, the green eco-friendly phytosome-based delivery system of the present invention provides a multifunction approach aiming to solve economic, environmental, and health issues.

[0106] More specifically, the results indicate that the phytosome-based delivery system of the present invention:

[0107] – improves the solubility of hydrophilic bioactive ingredients through the use of amphiphilic lipids;

[0108] – improves the physicochemical stability and protection of the bioactive ingredient loaded into the system;

[0109] – increases the encapsulation efficacy and loading capacity for both hydrophilic and lipophilic bioactive ingredients; and

[0110] – increases the bioavailability of the bioactive ingredients loaded into the system, to be administered by different routes.

[0111] The above-described subject matter is provided as an illustration of this invention and should not be interpreted in a limiting sense. The terminology used to describe preferred embodiments of this invention should not be construed to limit the invention to those particular embodiments.

[0112] As used in the description, definite and indefinite articles, in their singular form, are intended to encompass plural forms unless the context of the description explicitly indicates otherwise.

[0113] The indefinite articles “a” or “an” should generally be interpreted as “one or more” unless the sense of a singular embodiment is clearly defined in a specific situation.

[0114] It will be understood that the terms “comprise” and “include,” when used in this description, specify the presence of stated features, elements, components, steps, and operations but do not preclude the presence or addition of one or more other features, elements, components, steps, and operations.

[0115] As used throughout this patent application, the term “or” is used in an inclusive sense rather than an exclusive sense unless the exclusive sense is clearly defined in a specific situation. In this context, a phrase such as “X utilizes A or B” should be interpreted as including all relevant inclusive combinations.

[0116] All changes, as long as they do not modify the essential characteristics of the following claims, should be considered within the scope of protection of this invention.

[0117] The citation list is as follows:Non-Patent Literature

[0118] Ahmad, H., et al., Liposomes vs Phytosomes: Principles, Methodologies, and Therapeutic Applications with Emphasis on CNS Disorders on Nanopharmaceuticals: Principles and Applications, 2021, 1, 1.

[0119] Galanakis, C., et al., A knowledge base for the recovery of natural phenols with different solvents. Int. J. Food Prop. 2013. 16, 382-396.

[0120] Sarangi, M.K. and S. Padhi, Novel herbal drug delivery system: An overview. Arch. Med. Health Sci. 2018. 6, 171.

[0121] Fathi, F., et al., Exploring Gunnera tinctoria: From nutritional and anti-tumoral properties to phytosome development following structural arrangement based on molecular docking. Molecules, 2021, 26, 5935.

[0122] Fathi, F., et al., Formulation of nano / micro-carriers loaded with an enriched extract of coffee silverskin: physicochemical properties, in vitro release mechanism and in silico molecular modeling. Pharmaceutics, 2022, 14, 112.

Claims

A phytosome-based delivery systemcharacterized bycomprising:- physiologically compatible lipids selected from the group consisting of phosphoglycerides;- biocompatible and biodegradable lipids selected from the group consisting of glycerides and alcohol-based lipids; and- active ingredients selected from the group consisting of plant extracts and phytochemicals;wherein the mass ratio between the physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:20; andwherein the mass ratio between the active ingredients and the mixture of physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:50.The phytosome-based delivery system, according to claim 1,characterized bythe fact that the phosphoglycerides are selected from the group consisting of phosphatidylcholine, phosphatidylserine, and mixtures thereof.The phytosome-based delivery system, according to claim 1 or 2,characterized bythe fact that the glycerides are selected from the group consisting of triglycerides based on medium and long-chain fatty acids and sterols.The phytosome-based delivery system, according to claim 3,characterized bythe fact that the medium-chain triglycerides are selected from the group consisting of caprylic triglyceride, capric triglyceride, lauric triglyceride, and mixtures thereof.The phytosome-based delivery system, according to claim 3,characterized bythe fact that the long-chain triglycerides are selected from the group consisting of palmitic triglyceride, stearic triglyceride, oleic triglyceride, linoleic triglyceride, arachidonic triglyceride, eicosapentaenoic triglyceride, docosahexaenoic triglyceride, and mixtures thereof.The phytosome-based delivery system, according to claim 3,characterized bythe fact that the sterols are selected from the group consisting of cholesterol, ergosterol, phytosterols, stigmasterol, campesterol, beta-sitosterol, sitostanol, brassicasterol, and mixtures thereof.The phytosome-based delivery system, according to any of claims 1-6,characterized bythe fact that the alcohol-based lipids are selected from the group consisting of glycerol, propylene glycol, and mixtures thereof.The phytosome-based delivery system, according to any of claims 1-7,characterized bythe fact that the plant extracts are selected from the group consisting of coffee, silverskin, pomegranate peels, grape pomace, olive pomace,Arnica chamissonisand Cumin extracts.The phytosome-based delivery system, according to any of claims 1-8,characterized bythe fact that the phytochemicals are selected from the group consisting of phenolic, flavonoids, alkaloids, anthocyanins, fibers, vitamins and fatty acids.A method for obtaining the phytosome-based delivery system as disclosed in any of the claims 1-9,characterized bycomprising the steps of:a. dissolving the bioactive ingredient in ethanol or ethanolic aqueous solution;b. dissolving the physiologically compatible lipids in biocompatible and biodegradable lipids;c. mixing the solutions obtained from steps (a) and (b); andd. removing the excess of solvent;e. hydrating the phytosome obtained in step (d); andf. drying the hydrated phytosome obtained in step (e);wherein steps (a) and (b) can be performed in any order.The method, according to claim 10,characterized bythe fact that, in step (a), the mass ratio between the bioactive ingredient and the ethanol varies from 1:20 to 1:200.The method, according to any of claims 10 or 11,characterized bythe fact that, in step (a), the temperature varies from 0 to 60 ºC, preferably from 25 to 60 ºC.The method, according to any of claims 10-12,characterized bythe fact that, in step (b), the mass ratio between the physiologically compatible lipids and biodegradable lipids varies from 1:1 to 1:20.The method, according to any of claims 10-13,characterized bythe fact that, in step (b), the temperature varies from 0 to 60 ºC, preferably from 25 to 60 ºC.The method, according to any of claims 10-14,characterized bythe fact that, in step (c), the mass ratio between the active ingredients and the mixture of physiologically compatible lipids and the biocompatible and biodegradable lipids ranges from 1:1 to 1:50.The method, according to any of claims 10-15,characterized bythe fact that, in step (c), the temperature varies from 0 to 60 ºC, preferably from 25 to 60 ºC.The method, according to any of claims 10-16,characterized bythe fact that at least one of the steps (a), (b) and (c) are performed under stirring during 1 and 2 hours.The method, according to any of claims 10-17,characterized bythe fact that, in step (d), the phytosome obtained is allowed to rest from 6 to 12 hours after removing the excess of solvent.The method, according to any of claims 10-18,characterized bythe fact that, in step (e), the phytosome obtained in step (d) is hydrated by using water or an aqueous solution of either a positively or negatively charged natural polymer for coating.The method, according to claim 19,characterized bythe fact that the negatively charged natural polymers are at least one selected from the group consisting of pectin, alginate, starch, Arabic gum, maltodextrin, carboxylated chitosan, xanthan gum, casein, and mixtures thereof.The method, according to claim 19,characterized bythe fact that the positively charged natural polymers are at least one selected from the group consisting of zein, chitosan, and mixtures thereof.The method, according to any of claims 10-21,characterized bythe fact that, in step (f), the hydrated phytosome obtained in step (e) is dried by spray-drying or by freeze-drying.The method, according to any of claims 10-22,characterized bythe fact that the dried phytosome-based delivery system is used directly or loaded into solid lipid nanoparticles, nanostructured lipid carriers or nanoemulsions comprising at least one of the groups consisting of lipids, emulsifiers, and co-emulsifiers.A composition comprising the phytosome-based delivery system as disclosed in any of the claims 1-9,characterized bythe fact that it is in the form of powders, capsules, granules, pellets, tablets, creams, gels, ointments, pastes, suspensions, lotions, or syrups.A composition comprising the phytosome-based delivery system as disclosed in any of the claims 1-9 for topical or oral usecharacterized bythe fact that it is as a pharmaceutical, cosmetic or food product.

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