Compositions and formulations based on 12-carbon atom chain structures having broad-spectrum antimicrobial activity

Abstract

Novel compositions are described, each comprising at least one active constituent that has a 12-carbon atom backbone as a 12-carbon chain base structure having at least a sub-terminal nitrogen and no terminal amino group. One of the active constituents is Boc-12-Ado-OH (BOA) and / or N,N-dimethyldodecylamine N-oxide (LO). Novel particle or liposomal compositions comprising at least BOA and / or LO may be prepared with an emulsifier and / or lipid and optionally a biopolymer, and may be formulated into pharmaceutically acceptable formulations and / or medicaments with or without one or more pharmaceutically acceptable carriers or excipients for utilization as an antimicrobial against one or more microbial pathogens. The novel antimicrobial compositions have broad-spectrum growth inhibitory or other destructive activity against microbial pathogens, biofilms produced by one or more pathogens, and biofilm infections.

Description

[0001] Compositions and Formulations Based on 12-Carbon Atom Chain Structures Having Broad- Spectrum Antimicrobial ActivityFIELD OF THE INVENTION

[0002] Described herein are compositions for utilization as antimicrobials against pathogenic microbes, comprising at least one active constituent having a 12-carbon atom backbone as a 12-carbon base structure and at least a sub-terminal nitrogen as part of the backbone structure, which is not a terminal nitrogen nor a terminal amino group. The compositions herein unexpectedly exhibit growth inhibitory activity and / or antimicrobial activity against a broad-spectrum of pathogenic microbes that include bacterial pathogens, fungal pathogens and combinations thereof (which may or may not be resistant to an alternative anti-infective agent). The compositions do not require a surfactant for such activity nor do they require a coupling agent as described. Structures as described herein having the 12- carbon atom backbone structure and at least one nitrogen in the backbone structure that is not terminal were not expected nor predicted to be effective as an antimicrobial, and in particular, such structures were not expected to have activity against Gram-negative bacteria.BACKGROUND

[0003] Pathogenic microorganisms continue to evolve, proving difficult to treat. Ongoing identification and development of broad-spectrum antimicrobial agents, their useful compositions and formulations, remain necessary to combat resistance profiles of many of the more pathogenic microorganisms as well as newly emergent pathogenic microorganisms.

[0004] Fatty acid antimicrobials may prove to be a next generation (or "gen" herein) for anti- infectives. The medium chain saturated fatty acid with 12 carbon atoms, lauric acid, has been found to have a very weak inhibitory activity against certain Gram-positive bacteria when applied topically or when tested in vitro. To date, however, said fatty acids, while present in certain foods, are not readily internalized on their own, and are merely provided as a topical "anti-infective" for humans and animals. In vitro testing of lauric acid show some benefits, or show no potency, and most activity attributed to ingestion of foods containing lauric acid are actually attributed more to monolaurin (glycerol monolaurate, which is a monoglyceride). In vivo evidence of lauric acid activity when provided independently at physiologic pH values is lacking due to its insolubility and route of degradation in vivo, as it does not remain in a form associated with its inhibitory activity, which foils direct-acting activity. From in vitro testing, lauric acid appears to be inactive against Gram-negative bacteria (e.g., Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens, as representative examples). (See, Nagase S., et al., Comparison of the antimicrobial spectrum and mechanisms of organic virgin coconut oil and lauric acid against bacteria, J. Wellness Health Care 2017;41(l):87-95).

[0005] Derivatives of the 12-carbon fatty acid do not behave predictably or the same as lauric acid. Overall, the literature has been conflicted, and does not indicate any obvious or predictable use of a direct acting lauric acid as an effective antimicrobial against a broad-spectrum or broad assortment of pathogenic microorganisms. And, despite previous efforts direct acting agents with effective antimicrobial activity for in vivo utilization are still needed. Antimicrobial activity against biofilms in the body is also needed, as biofilms are believed to be involved in up to 80% of microbial infections and many of which are considered resistant to current antimicrobial / antibiotic treatments, according to the National Institutes of Health. (See, Camara M, et al., Economic significance of biofilms: a multidisciplinary and cross-sectoral challenge, NPJ Biofilms and Microbiomes, 2022, vol. 8, article number 42, https: / / doi.org / 10.1038 / s41522-022-00306-y).

[0006] There is a need for next gen fatty acids that deliver direct acting and effective antimicrobial activity. Methods for and formulations and / or medicaments that can be utilized in vivo safely and efficaciously are also needed.

[0007] There remains a need for a next gen direct acting antimicrobial utilized individually, independently, or with other antimicrobial agent(s) and, when utilized, provides sufficient or clinically useful therapeutic action against one or more harmful and / or infectious pathogens.

[0008] There remains a need for a next gen direct acting antimicrobial utilized individually, independently, or with other antimicrobial agent(s) and, when utilized, provides sufficient or clinically useful therapeutic action against a broad-spectrum of harmful and / or infectious pathogens, including Gram-positive bacteria, Gram-negative bacteria, and fungus or fungi, which may or may not be resistant to at least one alternative antimicrobial typically or previously indicated for therapeutic action against such a harmful and / or infectious pathogen.

[0009] There remains a need for a next gen direct acting antimicrobial utilized individually, independently, or with other antimicrobial agent(s) and, when utilized, provides sufficient or clinically useful therapeutic action against a harmful and / or infectious microbial biofilm, including biofilms produced by one or more Gram-positive bacteria, Gram-negative bacteria, and fungus or fungi, which may or may not be resistant to at least one alternative antimicrobial typically or previously indicated for therapeutic action against such a harmful and / or infectious pathogen.

[0010] There remains a need for a next gen direct acting antimicrobial utilized individually, independently, or with other antimicrobial agent(s) and, when utilized, provides a good safety profile.

[0011] There remains a need for a next gen direct acting antimicrobial utilized individually, independently, or with other antimicrobial agent(s) and, when utilized, has a status and / or notification as Generally Recognized As Safe (GRAS) (e.g., in compliance with or in association with at least the U.S. Food and Drug Administration and / or equivalent administration or organization outside the U.S.).

[0012] There remains a need for a next gen direct acting antimicrobial utilized at least individually, or independently, and, when so utilized, has antimicrobial activity or a growth inhibitory effect against one or more antibiotic resistant or drug resistant pathogens identified in a World Health Organization (WHO) Global Priority List, such as but not limited to: Acinetobacter baumannii (e.g., carbapenem- resistant strains; Priority 1), Pseudomonas aeruginosa (e.g., carbapenem-resistant strains; Priority 1), Enterobacteriaceae (e.g., carbapenem-resistant strains, ESBL-producing strains, such as Klebsiella pneumonia, Escherichia coli, Enterobacter spp., Serratia spp. Proteus spp., Providencia spp., Morganella spp.; Priority 1), Enterococcus faecium (e.g., vancomycin-resistant strains; Priority 2), Staphylococcus aureus (e.g., methicillin-resistant strains, vancomycin intermediate and resistant strains; Priority 2), Helicobacter pylori (e.g., clarithromycin-resistant strains; Priority 2), Campylobacter (e.g., fluoroquinolone-resistant strains; Priority 2), Salmonella spp. (e.g., fluoroquinolone-resistant strains; ; Priority 2), Neisseria gonorrhoeae (e.g., cephalosporin-resistant strains, fluoroquinolone resistant strains; Priority 2), Streptococcus pneumoniae (e.g., penicillin-non-susceptible strains; Priority 3), Haemophilus influenza (e.g., ampicillin-resistant strains; Priority 3), Shigella spp. (e.g., fluoroquinolone-resistant strains; Priority 3), and Mycobacteria. (See, https: / / www.who.int / news / item / 27-02-2017-WHO- publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed). A next gen direct acting antimicrobial described herein may be utilized at least individually or independently, and, when so utilized, has antimicrobial activity or growth inhibitory effect against one or more of such antibiotic resistant or drug-resistant bacteria identified by WHO, in which the next gen antimicrobial described herein complies with GRAS, is safe, and provides sufficient antimicrobial activity (e.g., inhibitory activity) for sufficient or clinically useful therapeutic action against the one or more of such harmful and / or infectious bacterial pathogens.

[0013] There remains a need for a next gen direct acting antimicrobial utilized at least individually, or independently, and, when so utilized, has antimicrobial activity or growth inhibitory effect or therapeutic effect against one or more fungal pathogens identified in a World Health Organization (WHO) Global Priority List, such as but not limited to: Candida albicans (critical priority); Aspergillus fumigatus (critical priority); Candida auris (critical priority); Cryptococcus neoformans (critical priority); Candida glabrata (e.g., Nakaseomyces glabrata; high priority); Histoplasma spp. (e.g., capsulatum; high priority); Eumycetoma causative agents (e.g., fungi causing mucormycosis or mycetoma; high priority); Fusarium spp. (high priority); Candida tropicalis (high priority); and Candida parapsilosis (high priority). (See. https: / / www.who. int / publications / i / item / 9789240060241). A next gen direct acting antimicrobial described herein may be utilized at least individually or independently, and, when so utilized, has antimicrobial activity or growth inhibitory effect against one or more of the fungal pathogens identified by WHO, in which the next gen antimicrobial described herein complies with GRAS, is safe, and providessufficient activity (e.g., inhibitory activity) for sufficient or clinically useful therapeutic action against the one or more of such harmful and / or infectious fungal pathogens.SUMMARY

[0014] Described herein are next generation direct-acting compositions, each next gen composition comprises an active constituent with a 12-carbon atom backbone, having a 12-carbon fatty acid base structure, and a sub-terminal nitrogen (N) on the fatty acid chain or backbone structure, which is not a terminal N containing side group (meaning there is no N-terminus to the start or end of the fatty acid chain, nor is an N-terminal end of the fatty acid, nor is there a terminal free amine or amino group, which is -NH2, at either end of the fatty acid chain. The 12-carbon base structure will require the 12-carbon atom chain, a nitrogen bound to a carbon at an end of the 12-carbon atom chain, and the nitrogen in the chain and forming part of the backbone structure being further bound to at least one other carbon (C) or oxygen (O) (in which the N, C and / or O may or may not contain further side chains), so that the nitrogen is not a terminus of the chain structure. Such an active constituent is also referred to herein as AFAC.

[0015] Boc-12-Ado-OH (also referred to as Boc-12-aminododecanoic acid or 12-(Boc- amino)dodecanoic acid; herein "BOA") is one AFAC utilized in a next gen composition described herein. BOA has a 12-carbon base structure, an alkane chain with terminal carboxylic acid and Boc-protected amino groups. The logP value of BOA is 4.89. BOA does not have a terminal free amino group, does not have an N terminus, does not have an N-terminal end.

[0016] N,N-dimethyldodecylamine N-oxide (also referred to as dodecyldimethylamine oxide or lauryldimethylamine oxide or lauramine oxide; herein "LO") is also an AFAC utilized in a next gen composition described herein. LO has a 12-carbon base structure, a tertiary amine oxide (via oxidation of an amino group) having a C12 alkyl tail. LO reacts with strong acids in exothermic reactions to form fatty acid salts plus water. The logP value of LO is 3.87. LO does not have a terminal free amino group, does not have an N terminus, does not have a N- terminal end.

[0017] In one or more embodiments, a next gen composition comprises one or more AFACs, in which the one or more AFACs is one comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen adjacent the 12-carbon atom backbone and part of the backbone, in which the nitrogen is not a terminal nitrogen and is not a terminal amino group, the next gen composition further comprising an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as further described herein), in a pharmaceutically acceptable or medically acceptable form. In one or more embodiments, a next gen composition comprises one or more AFACs, in which the one or more AFACs is one with a 12-carbon atom backbone having a 12-carbon atom chain and a sub-terminal nitrogen adjacent the 12-carbon atom backbone and part of the backbone, in which the nitrogen is not a terminal nitrogen nor a terminal amino group, and further comprises an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a pluralityof emulsifiers and / or lipids or types as described herein), and a biopolymer (or more than one biopolymer type or a plurality of biopolymers / biopolymer types as described herein), in a pharmaceutically acceptable or medically acceptable form. In one or more embodiments, such a next gen composition is caused to form a liposomal composition or liposomal like composition comprising liposomes, liposomal like particles, and / or small vesicles and / or optionally aggregates thereof, in which the liposomal composition or liposomal like composition comprises at least the AFAC (having a 12-carbon atom backbone and a 12-carbon base structure with a sub-terminal nitrogen as part of the backbone, which is not a terminal nitrogen nor a terminal amino group) and the emulsifier and / or lipid and optionally the biopolymer.

[0018] In one or more embodiments, a next gen composition comprises at least one AFAC and the AFAC is at least LO, and further comprises an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein), in a pharmaceutically acceptable or medically acceptable form. In one or more embodiments, a next gen composition comprises at least one AFAC, in which AFAC is at least LO, and further comprises an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein), and a biopolymer (or more than one biopolymer type or a plurality of biopolymers / biopolymer types as described herein), in a pharmaceutically acceptable or medically acceptable form. Such a next gen composition is caused to form a liposomal composition or liposomal like composition comprising liposomes, liposomal like particles, and / or small vesicles, and / or aggregates thereof, in which the liposomal composition or liposomal like composition comprises at least LO, the emulsifier and / or lipid and optionally the biopolymer.

[0019] In one or more embodiments, a next gen composition comprises at least one AFAC and the AFAC is at least BOA, and further comprises an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein), in a pharmaceutically acceptable or medically acceptable form. In one or more embodiments, a next gen composition comprises at least one AFAC and the AFAC is at least BOA, and further comprises at least an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein), and a biopolymer (or more than one biopolymer type or a plurality of biopolymers / biopolymer types as described herein), in a pharmaceutically acceptable or medically acceptable form. Such a next gen composition is caused to form a liposomal composition or liposomal like composition comprising liposomes, liposomal like particles, and / or small vesicles, and / or aggregates thereof, in which the liposomal composition or liposomal like composition comprises at least BOA, the emulsifier and / or lipid and optionally the biopolymer.

[0020] In one or more embodiments herein, a next gen composition herein having one or more AFACs is or comprises a liposomal composition or liposomal like composition comprising liposomes,liposomal like particles, and / or small vesicles and / or optionally aggregates thereof. As used herein, the term "liposomal composition" or "liposomal like composition" refers to a composition comprising liposomes and / or liposomal like particles, and / or small vesicles and / or optionally aggregates thereof, in which liposome refers to artificially prepared vesicles or vesicle like particles or micelles composed of one or more lipids and / or emulsifiers as further described herein and further comprising at least one AFAC, and optionally at least one biopolymer.

[0021] In one or more forms, any such a next gen composition as described above and elsewhere herein comprising a liposomal composition or liposomal like composition is for utilization against a pathogenic microbe and / or microbial infection or a suspected microbial infection caused by or suspected of being caused by one or more microorganisms considered harmful and / or infectious as an antimicrobial and / or for inhibiting growth of the microbe. In one or more forms, such a next gen composition is for utilization against a biofilm produced by one or more of such microorganisms considered harmful and / or infectious, or against a biofilm infection, such that utilization is for inhibition of formation and / or destabilization of the biofilm or as a treatment of the biofilm infection.

[0022] In one or more embodiments, any such next gen composition comprising a liposomal composition or liposomal like composition and / or particles and / or aggregates thereof as described herein may further comprise one or more excipients for their utilization against a microbial infection or a suspected microbial infection caused by or suspected of being caused by one or more microorganisms considered harmful and / or infectious. In one or more embodiments, any such next gen composition further comprises one or more excipients in a formulation for utilization against a biofilm produced by one or more microorganisms considered harmful and / or infectious or against a biofilm infection, the biofilm or infection being on one or more natural surfaces (e.g., tissue of a subject, as merely a representative example) and / or on one or more artificial surfaces (e.g., prostheses, medical device, catheter, as merely representative examples).

[0023] In one or more embodiments, are the delivering of at least one or more next gen compositions comprising liposomal composition or liposomal like composition and / or particles and / or aggregates thereof as described herein to a cell comprising contacting the cell with the one or more next gen compositions comprising at least one AFAC comprising a 12-carbon atom backbone having a 12- carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form with or without one or more pharmaceutically acceptable carriers and / or excipients. In one or more embodiments, the next gen compositions further comprise an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein) in a pharmaceutically acceptable form. The next gen compositions may further comprise a biopolymer (or more than one biopolymer type or a plurality of biopolymers or biopolymer types as described herein) in a pharmaceutically acceptableform. In one or more embodiments, the contacting the cell with the next gen composition includes providing the next gen composition to at least an outer membrane of a target cell in a subject in need thereof. In one or more embodiments, the subject in need thereof is a subject having or suspected of having microbial pathogen. In one or more embodiments, the subject in need thereof is a subject having or suspected of having a broad-spectrum of microbial pathogens (bacterial, fungal, drug-resistant, multidrug resistant, and any combination thereof). In one or more embodiments, the subject in need thereof is a subject having or suspected of having a biofilm infection from a bacterial and / or fungal source, and the bacteria and / or fungus or fungi may be a susceptible microorganism, drug-resistant, multi-drug resistant, and any combination thereof.

[0024] In one or more embodiments, described herein is one or more next gen compositions comprising a liposomal composition or liposomal like composition and / or particles and / or aggregates thereof as described herein, the liposomal composition or liposomal like composition and / or particles and / or aggregates thereof utilized for delivery to a cell comprising a means for delivery and / or a means for administering to a subject, in which the liposomal composition or liposomal like composition and / or particles and / or aggregates comprise at least one AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form with or without one or more pharmaceutically acceptable carriers and / or excipients and with or without one or more biopolymer. The liposomal composition or liposomal like composition and / or particles and / or aggregates further comprise an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as described herein) in a pharmaceutically acceptable form. In one or more embodiments, the subject is a subject in need thereof. In one or more embodiments, the subject has or is suspected of having a microbial pathogen. In one or more embodiments, the subject has or is suspected of having a broad-spectrum of microbial pathogens (bacterial, fungal, drug-resistant, multi-drug resistant, and any combination thereof). In one or more embodiments, the means for delivery and / or means for administering to a subject includes providing the one or more next gen compositions in one or more formulations sufficient for delivery or administering the one or more next gen compositions in the one or more formulations. In one or some embodiments, the means for delivery to a cell and / or means for administering to a subject includes providing the liposomal composition or liposomal like composition and / or particles and / or aggregates thereof in a medically acceptable or pharmaceutically acceptable form as at least one formulation for sufficient for effective delivery. In one or more embodiments, the means for delivery to a cell and / or means for administering to a subject includes safely and effectively administering the at least one formulation to the subject, such that over a period of time, the formulation provides antimicrobial activity and / or growth inhibitory activity against the microbial pathogen. The antimicrobial activity and / or growth inhibitory activity may be sufficient to reduce growth of themicrobial pathogen or may kill some or all of the microbial pathogen. The formulations may be delivered in a medical office, medical clinic or hospital setting, and the means for administering the at least one formulation to the subject is any pharmaceutical mode accepted in a medical office, medical clinic or hospital setting. In one or more embodiments, the means for delivery is by an inhalation means or by a pulmonary route. In one or more embodiments, the means for administering to a subject is by inhalation or by a pulmonary route. In one or more embodiments, the means for delivery is by an oral means. In one or more embodiments, the means for administering to a subject is oral, which may include small intestine, colon. In one or more embodiments, the means for delivery is by an intravenous means. In one or more embodiments, the means for administering to a subject is intravenous. In one or more embodiments, the means for delivery is by an intramuscular means. In one or more embodiments, the means for administering to a subject is intramuscular. In one or more embodiments, the means for delivery is by a transdermal means. In one or more embodiments, the means for administering to a subject is transdermal. In one or more embodiments, the means for delivery is by a parenteral means. In one or more embodiments, the means for administering to a subject is parenteral. In one or more embodiments, the means for delivery is by an intra nasal means. In one or more embodiments, the means for administering to a subject is intra nasal. In one or more embodiments, the means for delivery is by means of direct targeting to at least one location or site. In one or more embodiments, the means for administering to a subject is by site-specific targeting. In one or more embodiments, the means for delivery is by a subcutaneous means. In one or more embodiments, the means for administering to a subject is subcutaneous. In one or more embodiments, the means for delivery is by an intramucosal route and / or a rectal and / or vaginal means. In one or more embodiments, the means for administering to a subject is intramucosal and / or rectal and / or vaginal. In one or more embodiments, the means for delivery is by an enema means. In one or more embodiments, the means for administering to a subject is by enema. In one or more embodiments, the means for delivery is by a delivery system (e.g., beaded system, antibody system, gelation system, temperature-sensitive system, biodegradable system, scaffold system, polymer system, and any combination thereof). In one or more embodiments, the means for administering to a subject is utilizing such a delivery system as described.

[0025] In one or more embodiments, described herein is one or more next gen compositions comprising liposomal compositions or liposomal like compositions and / or particles and / or aggregates thereof as described herein in a formulation for use in medical therapy, the one or more next gen compositions comprising at least one AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form, with or without one or more pharmaceutically acceptable carriers and / or excipients. The one or more next gen compositions further comprise an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality ofemulsifiers and / or lipids or types as further described herein) in a pharmaceutically acceptable form and optionally a biopolymer (or more than one biopolymer type or a plurality of biopolymers or biopolymer types as further described herein), each in a pharmaceutically acceptable form. In one or more embodiments, the medical therapy includes use of a sufficient amount of the formulation in a subject. In one or more embodiments, the medical therapy includes therapeutic use of a therapeutically effective amount of the formulation in a subject in need thereof. The amount may be any one of a sufficient amount or an effective amount such that the formulation exhibits antimicrobial activity against a susceptible microbial pathogen or one described herein. The formulation is provided for a sufficient period of time with a foal of observing the antimicrobial activity as a growth inhibitory activity and / or killing of the susceptible microbial pathogen. The subject has or is suspected of having the susceptible microbial pathogen. In one or more embodiments, for use in medical therapy includes providing a sufficient and / or effective amount of the formulation and causing antimicrobial activity and / or growth inhibitory activity against the susceptible microbial pathogen. In one or more embodiments, for use in medical therapy includes providing an amount of the formulation as medical therapy to cause a change in growth or an inhibition in growth or a change in virulence of the susceptible microbial pathogen (bacterial, fungal, drug-resistant, multi-drug resistant and any combination thereof), which is sufficient to provide a "positive" clinical outcome in a subject or host (in which "positive" means that illness and / or clinical presenting symptoms and / or infection associated with the subject or host having or suspected of having the microbial pathogen has not progressed and / or is not worse and / or is clinically improved).

[0026] In one or more embodiments, one or more next gen compositions comprising liposomal compositions or liposomal like compositions and / or particles and / or aggregates thereof as described herein are provided in a formulation as a medicament comprising at least one AFAC comprising a 12- carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form with or without one or more pharmaceutically acceptable carriers and / or excipients. The one or more next gen compositions further comprise an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as further described herein) in a pharmaceutically acceptable form. In one or more embodiments, the one or more next gen compositions may further comprise a biopolymer (or more than one biopolymer type or a plurality of biopolymers or biopolymer types as further described herein) in a pharmaceutically acceptable form. In one or more embodiments, the medicament is for therapeutic use. In one or more embodiments, the therapeutic use comprises providing a sufficient amount of the formulation to a subject. In one or more embodiments, the therapeutic use comprises providing a therapeutically effective amount of the formulation. In one or more embodiments, the therapeutic use comprises providing a therapeutically effective amount of the formulation sufficient for activity against a susceptible microbial pathogen, selected from pathogenicbacteria, pathogenic fungus or fungi, drug-resistant pathogenic bacteria, drug-resistant pathogenic fungus or fungi, and any combination thereof. In one or more embodiments, the therapeutic use comprises providing a sufficient amount of the formulation sufficient for antimicrobial activity against a broad-spectrum of the susceptible microbial pathogen. In one or more embodiments, a therapeutically effective amount is an amount sufficient or effective to inhibit growth of the susceptible microbial pathogen and or kill at least a portion of the susceptible microbial pathogen reduction. In one or more embodiments, the formulation is in a sufficient amount to cause inhibition of growth the susceptible microbial pathogen and to cause a "positive" clinical outcome in a subject or host given the formulation (in which "positive" means that infection and / or clinical presenting symptoms in the subject has not progressed and / or is not worse or has clinically improved).

[0027] In one or more embodiments is a method for providing and / or administering one or more therapeutically effective next gen compositions comprising a liposomal composition or liposomal like composition and / or particles and / or aggregates thereof as described herein as a medicament to a subject, the method comprising providing the medicament to the subject in need thereof, the medicament comprising one or more next gen compositions comprising at least one AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen and is not a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form. The medicament further comprises an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as further described herein) in a pharmaceutically acceptable form. Optionally, the medicament may further comprise a biopolymer (or more than one biopolymer type or a plurality of biopolymers or biopolymer types as described herein) in a pharmaceutically acceptable form. The medicament may further comprise one or more pharmaceutically acceptable carriers and / or excipients. The medicament described herein is provided in an amount that is sufficient for growth inhibitory activity against susceptible microbial pathogens in the subject, the susceptible microbial pathogens including one or more of a pathogenic bacteria, pathogenic fungus or fungi, drug-resistant pathogenic bacteria, drug-resistant pathogenic fungus or fungi, and any combination thereof. The medicament may be utilized for treating the subject having or suspecting of having the susceptible microbial pathogen. In one or more embodiments, the medicament is provided in a sufficient amount to cause inhibition of growth the susceptible microbial pathogen and to cause a "positive" clinical outcome in a subject or host given the formulation (in which "positive" means that infection and / or clinical presenting symptoms in the subject has not progressed and / or is not worse or has clinically improved).

[0028] In some embodiments, described herein is a kit for delivering one or more next gen compositions to a cell, the kit comprising at least one or more next gen compositions comprising at least one AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminalnitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form or medically acceptable form with or without one or more one or more pharmaceutically acceptable carriers and / or excipients.

[0029] In some embodiments, described herein is a kit for use of one or more next gen compositions comprising a liposomal composition or liposomal like composition and / or lipid containing particles and / or aggregates thereof as described herein as a medicament, the kit comprising at least one of one or more next gen compositions comprising at least one AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO, in a pharmaceutically acceptable form or medically acceptable form with or without one or more one or more pharmaceutically acceptable carriers and / or excipients. The medicament may be in one or more formulations in the kit.

[0030] In any of said kits, the liposomal composition or liposomal like composition and / or lipid containing particles and / or aggregates thereof further comprise an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types as further described herein) in a pharmaceutically acceptable form or medically acceptable form. In any of said kits, the liposomal composition or liposomal like composition and / or lipid containing particles and / or aggregates thereof may optionally comprise a biopolymer (or more than one biopolymer type or a plurality of biopolymers or biopolymer types as further described herein) in a pharmaceutically acceptable form or medically acceptable form. In one or more embodiments, any of said kits may further comprise instructions for providing the medicament to a cell. In one or more embodiments, any of said kits may further comprise instructions for providing the medicament to a subject. In one or more embodiments, any of said kits may further comprise a means for providing the medicament to a cell, the means being a means for delivery to a cell, and may utilize a pharmaceutical mode accepted in a medical office, medical clinic or hospital setting for delivery of the medicament. In one or more embodiments, any of said kits may further comprise a means for providing the medicament to a subject, the means being a means for administering to a subject utilizing a pharmaceutical mode accepted in a medical office, medical clinic or hospital setting for administration of the medicament. In one or more embodiments, any of said kits may further comprise a means for diluting and / or for suspending and / or re-suspending and / or reconstituting the medicament with or without an appropriate suspending material or suspending solution. In one or more embodiments, any of said kit may further comprise instructions for use of the medicament.

[0031] In some embodiments, the formulation or the medicament described herein is provided in an amount that is sufficient for antimicrobial activity and / or growth inhibitory activity against at least a Gram-negative bacteria in the subject. The Gram-negative bacteria may be any one or more from the group including Acinetobacter baumannii, Campylobacter jejuni, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coll, Haemophilus influenza, Helicobacter pylori, Klebsiella oxytoca, Klebsiellapneumoniae, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica, Salmonella enteritidis, Serratia marcescens, and Shigella dysenteriae.

[0032] In some embodiments, the formulation or the medicament described herein is provided in an amount that is sufficient for antimicrobial activity and / or growth inhibitory activity against at least a Gram-positive bacteria in the subject. The Gram-positive bacteria may be selected from any one or more from the group including Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus anginosus.

[0033] In some embodiments, the formulation or medicament described herein is provided in an amount that is sufficient for antimicrobial activity and / or growth inhibitory activity against at least a fungal pathogen in the subject. The fungal pathogen may be selected from any one or more from the group including Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (e.g., fungi causing mucormycosis or mycetoma).

[0034] In one or more embodiments, one or more next gen compositions when formed or caused to be formed are in a form of lipid containing particles and / or aggregates of particles. The particles comprise one or more of an AFAC comprising a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group, and / or BOA and / or LO. Particles and / or aggregates of particles are formed when compositions contain at least one or more AFAC described herein with an emulsifier and / or lipid. Particles and / or aggregates of particles are also formed when compositions contain at least one or more AFAC with an emulsifier and / or lipid and a biopolymer. Particles may be liposomal or liposomal-like particles, and may be less than 1 pmeter, and may be considered to be nano-sized, also referred to herein as nanoparticles. In one or more of the embodiments herein, the one or more next gen compositions may be in a form of nanoparticles or liposomal nanoparticles. When formed as aggregates of particles, the aggregates may be nano-sized aggregates or may be micro-sized aggregates. In one or more embodiments herein, the one or more next gen compositions may be in a form of non-aggregated particles and / or aggregates thereof. In one or more embodiments herein, the particles and / or aggregates thereof are in a solution as a suspension solution comprising water or a weak acidic buffer or an isotonic solution, with or without one or more excipients. In one or more embodiments herein, the particles and / or aggregates thereof may be lyophilized or at least partially dried.

[0035] In one or more embodiments herein, a composition herein comprising said particles and / or aggregates (comprising at least one AFAC and at least one emulsifier / lipid with or without at least one biopolymer) thereof may be provided as a medicament in one or more pharmaceutically acceptable formulations and / or one or more medically acceptable formulations, such formulations being onesaccepted in at least one of a medical office, medical clinic and / or hospital setting for delivery and / or administering to a cell and / or a host and / or a subject. The providing and / or delivery and / or administering includes any means and / or methods known to one of skill in the art for providing and / or for delivery and / or for administering a medicament as a pharmaceutically acceptable formulation and / or medically acceptable formulation, as is also described elsewhere herein. In one or more embodiments, the providing and / or delivery and / or administering of the medicament will cause sufficient and / or effective antimicrobial activity against a pathogenic microbe suspected of residing in or on the cell and / or host and / or subject. In one or more embodiments, the providing and / or delivery and / or administering of the medicament will cause sufficient and / or effective growth inhibitory activity against the pathogenic microbe suspected of residing in or on the cell and / or host and / or subject, the pathogenic microbe being one or more of a bacterial pathogen, a fungal pathogen, a drug-resistant pathogen, a multi-drug resistant pathogen, and any combination thereof.

[0036] Providing and / or delivery and / or administering of the medicament as medical therapy may be once daily, twice daily, three times per day, four times per day, five times per day or six times per day, or may be continuous or in intervals, such as on a timing system. Delivery and / or administration will continue as needed, generally daily, with or without reductions in the amount (e.g., daily amount) or timing (e.g., daily dosing) of the delivery and / or administration of the next gen composition as a medicament and / or as medical therapy.

[0037] In some embodiments, next gen compositions comprising liposomes, liposomal like particles and / or aggregates thereof for utilization as described herein comprise at least one AFAC as described herein. In one or more embodiments, in addition to the AFAC, at least one emulsifier and / or lipid is an active constituent. In one or more embodiments, in addition to the AFAC, at least one biopolymer is an active constituent.

[0038] In some embodiments, next gen compositions for utilization as described anywhere herein comprise at least one AFAC as described herein and at least one emulsifier and / or lipid as described herein, and form and / or are caused to form liposomes or liposomal like particles and / or aggregates thereof and are in and / or maintained in a suspension.

[0039] In one or more embodiments, next gen compositions for utilization as described herein comprise at least one AFAC as described herein and at least one emulsifier and / or lipid as described herein and at least one biopolymer as described herein, and form and / or are caused to form liposomes or liposomal like particles and / or aggregates thereof and are in and / or maintained in a suspension.

[0040] In embodiments herein, one or more next gen compositions herein are at least emulsifier- and / or lipid -containing particles and / or emulsifier- and / or lipid -containing aggregates of particles thereof comprising one or more of an AFAC that comprise a 12-carbon atom backbone having a 12-carbon base structure and a sub-terminal nitrogen, which is not a terminal nitrogen nor a terminal amino group,and / or BOA and / or LO, in which the AFAC is between about 0.001 wt.% and about 30 wt.% or in any amount or range there between (based on total weight of composition in suspension). The amount of the AFAC when in such particles and / or aggregates thereof and provided in a suitable form as a medicament and / or for therapeutic utilization may be an amount that is sufficient for growth inhibitory activity of a susceptible microbial pathogen and / or for effective antimicrobial activity against one or more susceptible microbial pathogens described herein. The amount of emulsifier and / or lipid is between about 0.01 wt.% and about 50 wt.% of such compositions or in any amount or range there between or in an amount or range there between (based on weight of total composition in suspension). In one or more embodiments herein, the emulsifier- and / or lipid-containing particles and / or the emulsifier- and / or lipid- containing aggregates of particles thereof comprising one or moreAFACs described herein may further comprise one or more biopolymers. The biopolymer is in an amount between about 0.01 wt.% and about 45 wt.% of such compositions or in any amount or range there between or in an amount or range there between (based on weight of total composition) sufficient for effective antimicrobial activity against one or more microbial pathogens described herein.

[0041] The amount of the medicament and / or formulation provided for therapeutic utilization (e.g., to a subject or host) may be based on or may be adjusted after MIC calculations are obtained for a sample obtained that contains the susceptible microbial pathogen and is tested for susceptibility in a laboratory, which is a known and commonly utilized procedure performed by hospitals, medical offices and clinics.

[0042] An emulsifier may be one or more of an emulsifier, stabilizer, gelling agent or thickener as permitted in pharmaceuticals. Examples include but are not limited to lecithin, fat soluble vitamins, amino acids, cetostearyl alcohol, carrageenan, guar gum, xanthum gum, polysorbate, mono- and diglycerides of fatty acids, sucrose esters, sucroglycerides, polyglycerol esters of fatty acids, polyglycerol polyricinoleate, stearoyl lactylates, and sorbitan esters. A natural emulsifier derived from either a vegetable source (examples including but not limited to acacia, tragacanth, alginates, Chondrus, xanthan, and pectin) or an animal source (examples including but not limited to gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin) are useful as these materials form hydrophilic colloids when added to water. The emulsifier may also be a finely dispersed solid (dispersed to a sufficiently fine powder) that form particulate films around a dispersed droplet (such as colloidal clays, bentonite, veegum / magnesium aluminum silicate).

[0043] A lipid is any one or more of a biologically compatible phospholipid or phosphatide (e.g., phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidic acid (PA), phosphatidylcholine (PC), and / or phosphatidylserine (PS), and any combinations thereof), a lysophospholipid (e.g., lyso- phosphatidylethanolamine (LPE), sphingomyelin (SPM), and any combination thereof), lecithin, lecithin components (naturally occurring components, such as one or more naturally occurring phospholipids(e.g., PC, PE, PI, PA, PS) and / or one or more naturally occurring lysophospholipids (e.g., LPE, SPM)), and may also include one or more of a bulky fatty acid (e.g., cholesterol, lipid or fatty acid having a chain length predominantly from about C-14 to C-20, choline, and choline esters), and triglycerides, and / or carbohydrates), and any combination thereof. In one or more embodiments, the lipid comprises or is predominantly a lecithin. In one or more embodiments, the lipid may comprise or is predominantly PC (e.g., L-a-phosphatidylcholine), or may be PC in combination with other phosphatides (e.g., acetone insoluble phospholipids). In one or more embodiments, the lipid is or is predominantly amphiphilic. In one or more embodiments, the lipid (or lecithin) may be combined with at least one bulky fatty acid, such as cholesterol and / or lipids / free fatty acids including ones having a chain length predominantly from about C-14 to C-20. In one or more embodiments, the lipid is a mixture of naturally occurring phospholipids (two or more of PC, PE, PI, PA, and / or PS). In one or more embodiments, the lipid may be or may include PC, with any one or more of at least one other phospholipid, with or without cholesterol. The lipid is from a natural source, such as an animal or plant. The lipid may be sourced from and / or be in a granular form (e.g., L-al pha-lecithin granules).

[0044] In one or more embodiments, lecithin is a complex mixture of acetone-insoluble phosphatides fi.e., phospholipids), which consist of PC, PE, PI, and PA, present with various amounts of other substances such as triglycerides, fatty acids, and carbohydrates, as separated from the crude vegetable oil source. The lecithin often contains not less than 50% of acetone-insoluble matter. In one or more embodiments, lecithin is described as and may be selected from the group consisting of soybean lecithin, hydrogenated soybean lecithin, dilauroyl lecithin, dimyristoyl lecithin, dipalmitoyl lecithin, distearoyl lecithin, l-myristoyl-2-palmitoyl lecithin, l-palmitoyl-2-myristoyl lecithin, l-palmitoyl-2- stearoyl lecithin, l-stearoyl-2-palmitoyl lecithin, yolk lecithin, dioleoyl lecithin, dilauroyl phosphatidylglycerol, dipalmitoyl phosphatidic acid, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidyl serine, dipalmitoyl phosphatidyl di-serine, dipalmitoyl phosphatidylcholine, phosphatidylcholine (e.g., L-a-phosphatidylcholine), brain phosphatidyl serine, brain sphingomyelin, dipalmitoyl sphingomyelin, distearoyl sphingomyelin, distearoyl phosphatidylethanolamine (DSPE), or any combination thereof.

[0045] In one or more embodiments, the emulsifier and / or lipid in a next gen composition described herein, one comprising liposomes, liposomal like particles and / or aggregates thereof, is in an amount between about 0.01 wt.% and about 50 wt.%, based on total weight of the composition, or in any range therebetween. For example, the emulsifier and / or lipid may be in an amount between about 0.01 wt.% and about 20 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.01 wt.% and about 10 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.01 wt.% and about 5 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amountbetween about 0.01 wt.% and about 1 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.1 wt.% and about 20 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.1 wt.% and about 10 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.1 wt.% and about 5 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.1 wt.% and about 1 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount between about 0.1 wt.% and about 0.5 wt.%, or between about 0.5 wt.% and about 20 wt.%, or between about 0.5 wt.% and about 10 wt.%, or between about 0.5 wt.% and about 5 wt.%, or between about 0.5 wt.% and about 1 wt.%, or between about 1 wt.% and about 40 wt.%, or between about 1 wt.% and about 30 wt.%, or between about 1 wt.% and about 20 wt.%, or between about 5 wt.% and about 25 wt.%, or between about 10 wt.% and about 50 wt.%, based on total wet weight of the composition. The emulsifier and / or lipid may be in an amount less than 20 wt.%, based on total wet weight of the composition, or less than 10 wt.%, based on total wet weight of the composition, or less than 5 wt.%, based on total wet weight of the composition.

[0046] In one or more embodiments, the biopolymer is a copolymer. The biopolymer herein is often preferred as one that promotes a longer circulation time of a next gen composition described herein as a long-circulating liposomal composition or long-circulating liposomal like composition or one comprising particles and / or aggregates thereof as describe herein that contain at least one AFAC as described herein. In one or more embodiments, the biopolymer modifies the surface of a liposomal composition or liposomal like composition or one comprising lipid containing particles and / or aggregates thereof as describe herein that contain at least one AFAC as described herein and promotes prolonging circulating time of the liposomal composition or liposomal like composition or one comprising lipid containing particles and / or aggregates thereof. In one or more embodiments, the biopolymer is chitosan. In one or more embodiments, the biopolymer is unmodified chitosan. In one or more embodiments, the chitosan is deacetylated chitosan (e.g., >50% deacetylated). In one or more embodiments, the biopolymer is cellulose. In one or more embodiments, the biopolymer is alginate. In one or more embodiments, the biopolymer is pectin. In one or more embodiments, the biopolymer (or, e.g., chitosan or cellulose or alginate or pectin), when provided with at least the one or more AFACs and the one or more emulsifier and / or lipid(s), has broad-spectrum activity and is so combined without requiring modification of the biopolymer (meaning the biopolymer is not manipulate by requiring use of charged version, such as glycol chitosan, and is not manipulated by requiring a charged environment, such as by mixing or blending in an alkaline pH, or at a pH greater than pH 8 or at pH 9 or more).

[0047] In many embodiments, the biopolymer (or, e.g., chitosan or cellulose or alginate or pectin), when provided with one or more AFACs and at least one or more emulsifier and / or lipid(s), is so combined without grafting (i.e., without a grafting step or a further coupling reaction or coupling step, such as stepsthat occur with and are mediated by and require one or more known coupling agents, in which coupling agents include but are not limited to carbodiimide and / or N-hydroxysuccinimide, and the like, as are known by one of skill in the relevant art). In one or more embodiments, the biopolymer (e.g., chitosan, cellulose, alginate, and / or pectin), when provided with at least one AFAC and at least one emulsifier and / or lipid(s), is so combined without a further chemical cross-linking step or a further coupling reaction, so is not mediated by nor requiring one or more cross-linking agents and / or coupling agents, in which representative cross-linking agents include but are not limited to tripolyphosphate, molybdate, polyoxometalates, sulfate, phytate, dialdehydes, diepoxy polyethylene glycole dicarboxylic acid polyethylene glycole, and the like as are known by one of skill in the relevant art. In one or more embodiments, the biopolymer (e.g., chitosan, cellulose, alginate, and / or pectin), when provided with at least one AFAC and one or more emulsifier and / or lipid(s), is so combined without grafting (e.g., a grafting step), not requiring a further chemical cross-linking step nor a further coupling reaction.

[0048] In one or more embodiments, the biopolymer (or, e.g., chitosan or cellulose or alginate or pectin, et al.) in a next gen composition comprising liposomes, liposomal like particles and / or aggregates thereof is in an amount between about 0.01 wt.% and about 45 wt.%, based on total weight of the composition. For example, the biopolymer may be in an amount between about 0.01 wt.% and about 10 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount between about 0.01 wt.% and about 5 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount between about 0.01 wt.% and about 1 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount between about 0.01 wt.% and about 0.5 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount between about 0.01 wt.% and about 0.1 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount between about 0.1 wt.% and about 20 wt.%, or about 0.1 wt.% and about 10 wt.%, or about 0.1 wt.% and about 5 wt.%, or about 0.1 wt.% and about 1 wt.%, or about 0.5 wt.% and about 20 wt.%, or about 0.5 wt.% and about 10 wt.%, or about 0.5 wt.% and about 5 wt.%, or about 0.5 wt.% and about 1 wt.%, or about 1 wt.% and about 20 wt.%, or about 5 wt.% and about 20 wt.%, or about 5 wt.% and about 30 wt.%, or about 5 wt.% and about 40 wt.%, based on total wet weight of the composition. The biopolymer may be in an amount less than 10 wt.%, based on total wet weight of the composition, or less than 5 wt.%, based on total wet weight of the composition, or less than 1 wt.%, based on total wet weight of the composition.

[0049] In one or more embodiments, one or more next gen compositions each comprise liposomes and / or liposomal like particles and / or aggregates thereof as described herein, and the liposomes and / or liposomal like particles and / or aggregates thereof comprise one or more AFAC described herein, one or more lipids and / or emulsifiers described herein, one or more biopolymer described herein, and a suspension solution, which may be water (e.g., sterile water or distilled water or pure water) or a mildY1acidic buffer or an isotonic solution (e.g., normal saline solution, dextrose solution, Ringer's solution, lactated Ringer's solution) or a hypotonic solution (e.g., hypotonic saline solution, hypotonic dextrose solution) or a hypertonic solution (e.g., hypertonic saline solution, hypertonic dextrose solution) or a phosphate buffered saline solution, in which a next gen composition is in and / or may be suspended in the suspension solution and / or maintained and / or stored in the suspension solution. Storage may be at a refrigeration temperature and in a dark container or one that prevents light from passing through. The one or more AFACs will be in an amount between about 0.001 wt.% and about 30 wt.% or in any amount or range there between (based on wet weight of the composition). The one or more lipids and / or emulsifiers will be in an amount between about 0.01 wt.% and about 50 wt.% of the compositions or in any amount or range there between (based on wet weight of the composition). The one or more biopolymers will be in an amount between about 0.01 wt.% and about 45 wt.% of the compositions or in an amount or range there between (based on wet weight of the composition). The suspension solution will be in an amount between about 50 wt.% and about 99.9 wt.% of the compositions or in any amount or range there between (based on wet weight of the composition).

[0050] The next gen compositions and / or formulations thereof may be utilized as an antimicrobial agent for growth inhibitory activity against a Gram-negative bacterial pathogen susceptible to the next gen composition and / or utilized as described herein, the bacterial pathogen being selected from one or more from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL- producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL-producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem-resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem- resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains).

[0051] The next gen compositions and / or formulations thereof may be utilized as an antimicrobial agent for growth inhibitory activity against a Gram-positive bacterial pathogen susceptible to the next gen composition and / or utilized as described herein, the bacterial pathogen being selected from one or more from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistantstrains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes (including penicillin-non-susceptible strains), Streptococcus anginosus (including penicillin-non- susceptible strains).

[0052] The next gen compositions and / or formulations thereof may be utilized as an antimicrobial agent for growth inhibitory activity against a fungal pathogen susceptible to the next gen composition and / or utilized as described, selected from one or more from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (e.g., fungi causing mucormycosis or mycetoma).

[0053] In any one or more of the embodiments herein, microbial pathogens may be one of or any combination of bacterial pathogens and fungal pathogens, including ones considered resistant to a current anti-infective (e.g., drug-resistant or multi-drug resistant), as well as ones identified by a WHO Global Priority List or considered to be of local or global priority.

[0054] Unpredictably, one or more next gen compositions described herein overcome previous difficulties with internal use of fatty acids, and, in inventive ways described herein, meet at least one or more needs described above, such as becoming an effective, direct acting antimicrobial agent with sufficient antimicrobial properties for good and effective antimicrobial activity against microbial pathogens selected from one or more of a Gram-positive bacteria, Gram-negative bacteria, and fungus or fungi, as well as drug-resistant variants or drug-resistant strains, and a biofilm produced by the microbial pathogen and / or a microbial biofilm infection, and any combination thereof. In one or more embodiments, such microbial pathogens if antibiotic-resistant may be any one or more identified by a WHO Global Priority List or considered to be of priority for treatment against and / or for eradiation.

[0055] In one or more embodiments, a next gen composition and / or formulation and / or medicament thereof described herein is an effective, direct acting composition and / or formulation and / or medicament with sufficient and / or effective antimicrobial properties to cause harm or disruption to a microbial pathogen and / or a microbial biofilm and / or a microbial biofilm infection when utilized against the microbial pathogen and / or a microbial biofilm and / or a microbial biofilm infection (e.g., for medical therapy and / or clinical therapy). In view of the sufficient and / or effective antimicrobial activity of next gen compositions and / or formulations and / or medicaments thereof described herein against a broad-spectrum of microbial pathogens and against microbial biofilms and microbial biofilm infections, the novel next compositions described herein are to be considered as suitable alternative antimicrobial agents, particularly against pathogens considered resistant to one or more alternative and / or currently used antimicrobial or antibiotic.

[0056] In one or more embodiments is a liposomal composition comprising: an active constituent that contains 12 carbon atoms in a chain base structure with a nitrogen atom attached to one carbon of the 12 carbon atoms in the chain base structure, the nitrogen atom forming a part of the chain base structure and further attached to at least one of a separate carbon and an oxygen so that the nitrogen atom is not a terminal nitrogen atom and is not at any terminus of the active constituent, the active constituent lacking any amine group at any end or terminus of the active constituent, wherein the active constituent is in an amount between about 0.001 wt.% and about 30 wt.% based on total weight of composition in a suspension; a lipid selected from one or more from the group consisting of lecithin, phosphatidylcholine (PC), concentrated lecithin containing up to 25% PC, concentrated lecithin containing up to 40% PC, a mixture of glycerophospholipids, a phosphatide mixture comprising 25% to 95% PC, a lecithin containing acetone insoluble phosphatides, and combinations thereof, wherein the lipid is in an amount between about 0.01 wt.% and about 50 wt.% based on total weight of the liposomal composition in the suspension; a biopolymer comprising one or more from the group consisting of monosaccharide, polysaccharide, and mixtures thereof, wherein the biopolymer is in an amount between about 0.01 wt.% and about 40 wt.% based on total weight of the liposomal composition in suspension; and a suspension solution, wherein the suspension solution is in an amount between about 50 wt.% and about 99.9 wt.% based on total weight of the liposomal composition in the suspension.

[0057] In any of the liposomal compositions described, the suspension solution may be selected from the group consisting of sterile water, distilled water, pure water, a mild acidic buffer, an isotonic solution, normal saline solution, dextrose solution, Ringer's solution, lactated Ringer's solution, a hypotonic solution, hypotonic saline solution, hypotonic dextrose solution, a hypertonic solution, hypertonic saline solution, hypertonic dextrose solution and a phosphate buffered saline solution. In any of the liposomal compositions described, the biopolymer may selected from one or more from the group consisting of a chitosan, a cellulose, a hydroxypropyl methylcellulose, a carrageenan, an alginate, a guar gum, a polylysine, a poly(L)lysine,poly(L-glutamic acid, a poly(hyroxyethyl-l-asparagine, a xanthum gum, a gellan gum, a mixture of monosaccharides, starch, pectin, low methoxyl pectin, and pullulan. In any of the liposomal compositions described, the lecithin may contain a mixture selected from two or more from the group consisting of phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, phosphatidic acid, phosphatidylserine, lysophospholipids bulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, carbohydrates, and any combination thereof. In any of the liposomal compositions described, the phosphatide mixture contains phospholipids selected from the group consisting of glycerophospholipids, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, phosphatidic acid, phosphatidylserine, sphingomyelin, sphingolipids, lecithin, and any combination thereof. In any of the liposomal compositions described, the biopolymer is deacetylated chitosan, and the deacetylatedchitosan is any one or more of a low molecular weight chitosan, a medium molecular weight chitosan, and a high molecular weight chitosan. The liposomal composition may further comprise one or more pharmaceutically acceptable excipients. The liposomal composition may be one or more of a pharmaceutical composition and a medicament. The liposomal composition may be part of a kit comprising the liposomal composition in a pharmaceutically acceptable formulation, and instructions for use of the pharmaceutically acceptable formulation. In any of the liposomal compositions described, the active constituent is at least one from the group selected from 12-(Boc-amino)dodecanoic acid and N,N- dimethyldodecylamine N-oxide.

[0058] The liposomal composition may be in a formulation utilized as an antimicrobial against one or more Gram-negative bacterial pathogens selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL-producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL- producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem- resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL- producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem-resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinoloneresistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains).

[0059] The liposomal composition may be in a formulation utilized as an antimicrobial against one or more Gram-positive bacterial pathogens selected from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin- resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes (including penicillin-non-susceptible strains), Streptococcus anginosus (including penicillin-non-susceptible strains).

[0060] The liposomal composition may be in a formulation utilized as an antimicrobial against one or more fungal pathogens selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma).

[0061] The liposomal composition may be in a formulation utilized to disturb or inhibit formation of a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae. The liposomal composition may be in a formulation utilized as an antimicrobial against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae. The liposomal composition and / or nanoparticles comprising liposomal compositions are formed or caused to be formed after performing a method that comprises vigorously stirring the active constituent, the lipid and the biopolymer in the suspension solution for up to 24 hours and collecting nanoparticles formed after a filtration step, wherein the nanoparticles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, aggregates thereof, and combinations thereof.

[0062] In any one or more embodiments is an antimicrobial composition comprising: an active constituent, wherein the active constituent is selected from a group consisting of 12-(Boc- amino)dodecanoic acid (BOA) and any tautomeric forms of BOA, wherein BOA has a structure (1)H 9jpjd, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide; wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against a pathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

[0063] In any one or more embodiments is an antimicrobial composition comprising: an active constituent, wherein the active constituent is selected from a group consisting of N,N- dimethyldodecylamine N-oxide (LO) and any tautomeric forms of LO, wherein LO has a structure (2)(2); a lipid, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide; wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against apathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

[0064] In one or more embodiments is a medicament for use as an antimicrobial, the medicament comprising: an active constituent, wherein the active constituent is selected from one or more from a group consisting of: (a) 12-(Boc-amino)dodecanoic acid (BOA) and any tautomeric forms of BOA, whereinBOA has a structure (1)(1); and (b) N,N-dimethyldodecylamine N-oxide(LO) and any tautomeric forms of LO, wherein LO has a structure (2):CH3(2); a lipid, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide; wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against a pathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

[0065] In any of the antimicrobial compositions and / or medicaments described, the pathogenic microorganism may selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-negative bacteria selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL-producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL-producing strains), Enterobacter cloacae (including carbapenem- resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem-resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem-resistant strains, ESBL- producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains), and combinations thereof. In any of the antimicrobial compositions described, the pathogenic microorganism may selected from one or more from the group consisting of Gram-positive bacteria,Gram-negative bacteria, and fungus, and wherein the Gram-positive bacteria is selected from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes (including penicillin-non-susceptible strains), Streptococcus anginosus (including penicillin-non- susceptible strains), and combinations thereof. In any of the antimicrobial compositions described, the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the fungus is selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma), and combinations thereof. In any of the antimicrobial compositions described, the antimicrobial composition may be in a formulation utilized to disturb or inhibit formation of a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae, and combinations. In any of the antimicrobial compositions described, the antimicrobial composition may be in a formulation and utilized against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

[0066] In any of the antimicrobial compositions and / or medicaments described, the biopolymer is selected from one or more from the group consisting of chitosan, cellulose, hydroxypropyl methylcellulose, carrageenan, alginate, guar gum, polylysine, poly(L)lysine, poly(L-glutamic acid), poly(hyroxyethyl-l-asparagine, xanthum gum, gellan gum, a mixture of monosaccharides including L- fucose, galactose, glucose and glucuronic acid, starch, pectin, low methoxyl pectin, and pul lu Ian.

[0067] In any of the antimicrobial compositions and / or medicaments described, the lipid may be from an animal or plant source and is selected from one or more from the group consisting of phosphatidylcholine (PC); PC mixed with other phosphatides, in which PC is up to 25% of the mixture; PC mixed with other phosphatides, in which PC is up to 40% of the mixture; lecithin; lecithin comprising acetone insoluble phospholipids; concentrated lecithin; a combination of one or more lecithin components selected from the group consisting of phosphatidylethanolamine, phosphatidylinositol, PC, phosphatidic acid, phosphatidylserine, lysophospholipids, bulky fatty acids, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, and carbohydrates; a combination selected from one or more from the group consisting of glycerophospholipids, lysophospholipids, bulky fatty acids, sterols, fatty acids having a chain length predominantly from aboutC-14 to C-20; a mixture of naturally occurring glycerophospholipids; PC combined with one or more from the group selected from bulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, carbohydrates; a lecithin concentrate in which PC is up to 25% of the concentrate; a lecithin concentrate in which PC is up to 40% of the concentrate.

[0068] In any of the antimicrobial compositions and / or medicaments described, the antimicrobial compositions and / or medicaments may further comprise one or more pharmaceutically acceptable excipients selected from the group consisting of suspending solution, sugar, starch, cellulose, fat, wax, paraffin, oil, glycol, fatty acid ester, buffering agent, filler, absorbent, binder, humectant, disintegrating agent, lubricant, releasing agent, preservative, and coating agent, sweetener, colorant, flavorant, and antioxidant.

[0069] In any of the liposomal composition and / or any of the antimicrobial compositions and / or any of the medicaments described, each of the liposomal compositions, the antimicrobial compositions, and the medicament may be utilized in a formulation for one or more from the groups selected from: (a) delivering as an antimicrobial to one or more target pathogenic microbial cells; (b) providing as an antimicrobial to an outer membrane of one or more target pathogenic microbial cells; (c) delivering to one or more target pathogenic microbial cells by administering to a subject having or suspected of having the target pathogenic microbial cells; (d) providing as an antimicrobial for therapeutic use against one or more target pathogenic microbial cells; (e) providing as an antimicrobial for inhibiting growth of one or more target pathogenic microbial cells; and (f) providing in a kit having instructions for use. In any of the liposomal composition and / or any of the antimicrobial compositions and / or any of the medicaments described, the formulation may be sufficient for administering as at least one or more doses to a subject in need, the administering being selected from any one or more from the group consisting of orally, rectally, parenterally, intracisternally, intramuscularly, intravaginally, intraperitoneally, topically, bucally, nasally, or by enema.

[0070] These and other embodiments are described herein.DESCRIPTION OF REPRESENTATIVE EMBODIMENTS

[0071] Although making and using various embodiments are discussed in detail below, it should be appreciated that as described herein are provided many inventive concepts that may be embodied in contexts outlined and / or contemplated herein and / or interpreted or varied by the skilled artisan. Embodiments described herein are merely representative and do not limit the scope of the invention.

[0072] For each next gen composition, the composition comprises an AFAC with at least a 12- carbon atom backbone and having an uninterrupted 12-carbon chain base structure, along with a subterminal nitrogen (N), which is not a terminal N or a terminal side group containing an amino or amine group (meaning there is no N-terminus to the start or end of the constituent chain, nor is there an N- terminal end of the AFAC, nor is there a terminal free amine or amino group, which is -NH2, at either endof the AFAC). Sub-terminal means the nitrogen is not a terminal nitrogen nor is it a primary amine, the nitrogen may be and often is adjacent a terminal end of the chain, in which the terminal end may be or may contain oxygen (O) or carbon (C). Thus, for the constituent to be active, there is a nitrogen in the chain or backbone structure, but the N is not on either end or terminus of the constituent. In some embodiments, one terminus of the AFAC is a carboxylic acid. In some embodiments, one terminus of the AFAC is a methyl group. In some embodiments, one terminus of the AFAC is an amine oxide. In some embodiments, the AFAC is an amino fatty acid, in which an amino portion is not at an end or terminus of the constituent.

[0073] The base structure of a next gen AFAC will require a 12-carbon chain, a nitrogen bound to one end the 12-carbon chain, and near or adjacent a terminal oxygen or terminal carbon (which may or may not contain further side chains). Thus, N is not a terminus of the AFAC.

[0074] The AFAC in a next gen composition described herein is in an amount between about 0.001 wt.% and about 30 wt.% or in any amount or range there between (based on total weight of composition in suspension) and as described earlier in the Summary.

[0075] One next gen composition may include an AFAC as Boc-12-Ado-OH or Boc-12- aminododecanoic acid or 12-(Boc-amino)dodecanoic acid (or "BOA" herein). BOA has a 12-carbon base structure, an alkane chain with terminal carboxylic acid and Boc-protected amino groups. The terminal carboxylic acid can react with primary amine groups in the presence of strong activators or coupling agents (e.g. l-ethyl-3-carbodiimide (EDC), or hexafluorophosphate azabenzotriazole tetramethyl uranium (HATU)) to form a stable amide bond. BOA as shown below does not have a terminal N or amino group and does not have a primary amine. The logP value of BOA is 4.89. A representative structure for BOA is depicted as (I). It should be understood that the BOA described herein may exhibit the phenomenon of tautomerism, and the chemical structure (I) represents one of the possible tautomeric forms. Thus, it is understood that BOA as described herein encompasses any tautomeric form of the structure (I) illustrated below.

[0077] BOA is not a fatty acid ester. BOA is not a mono- or diglyceride of a fatty acid. BOA is an amino fatty acid. BOA on its own is not anticipated or predicted to have antimicrobial activity. BOA on its own has not been identified as an active antimicrobial fatty acid that can be internalized by a subject and then exhibit antimicrobial activity against a microbial pathogen residing in (or suspected of residing in) the subject. BOA on its own is not used as an antimicrobial agent nor is it predicted, on its own, to exhibit antimicrobial activity against a plurality of microbial pathogens. BOA on its own is not predicted to exhibit broad-spectrum antimicrobial activity against one or more microbial pathogens selected frompathogenic bacteria, pathogenic fungus or fungi, drug-resistant pathogenic bacteria, drug-resistant pathogenic fungus or fungi, and any combination thereof.

[0078] A next gen composition comprises at least one AFAC comprising at least BOA and further comprising an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein), the BOA and the emulsifier and / or lipid are each in a pharmaceutically acceptable or medically acceptable form. The BOA and emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein) are so combined in a manner to form or are caused to be formed into liposomes or liposomal like particles and / or aggregates thereof, and form at least liposomal compositions and / or liposomal like compositions.

[0079] A next gen composition may comprise at least one AFAC comprising at least BOA, an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein), and a biopolymer (or plurality of biopolymers), each in a pharmaceutically acceptable or medically acceptable form. The BOA, one or more emulsifiers and / or lipids and one or more biopolymers are so combined in a manner to form or are caused to be formed into liposomes or liposomal like particles and / or aggregates thereof, and form at least liposomal compositions and / or liposomal like compositions.

[0080] Another next gen composition includes an AFAC as N,N-dimethyldodecylamine N-oxide or dodecyldimethylamine oxide or lauryldimethylamine oxide or lauramine oxide (or "LO" herein). LO has a 12-carbon base structure, a tertiary amine oxide (via oxidation of an amino group) and a C12 alkyl tail. LO reacts with strong acids in exothermic reactions to form salts plus water. LO as shown below does not have a terminal N or amino group and does not have a primary amine. The logP value of LO is 3.87. A representative structure for LO is depicted as (II). It should be understood that the LO described herein may exhibit the phenomenon of tautomerism, and the chemical structure (II) represents one of the possible tautomeric forms. Thus, it is understood that LO as described herein encompasses any tautomeric form of the structure (II) illustrated below.

[0082] LO is not a fatty acid ester. LO on its own has not been identified as an active antimicrobial fatty acid that can be internalized by a subject and then exhibit antimicrobial activity against a microbial pathogen residing in (or suspected of residing in) the subject. LO on its own is not used as an internalized broad-spectrum antimicrobial agent nor is it predicted, on its own, to exhibit antimicrobial activity against a plurality of microbial pathogens when internalized by a subject. LO on its own is not predicted to exhibit broad-spectrum antimicrobial activity against one or a plurality of microbial pathogens selected from pathogenic bacteria and pathogenic fungus or fungi (including drug-resistant variants or strains).

[0083] A next gen composition may also comprise at least one AFAC comprising at least LO and further comprising an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein), the LO and the emulsifier and / or lipid are each in a pharmaceutically acceptable or medically acceptable form. The BOA and emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein) are so combined in a manner to form or are caused to be formed into liposomes or liposomal like particles and / or aggregates thereof, and form at least liposomal compositions and / or liposomal like compositions.

[0084] A next gen composition may also comprise at least one AFAC comprising at least LO, an emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein), and a biopolymer (or plurality of biopolymers), each in a pharmaceutically acceptable or medically acceptable form. The LO, emulsifier and / or lipid (or more than one emulsifier and / or lipid type or a plurality of emulsifiers and / or lipids or types thereof as described herein) and biopolymer (or plurality of biopolymers) are so combined in a manner to form or are caused to be formed into liposomes or liposomal like particles and / or aggregates thereof, and form at least liposomal compositions and / or liposomal like compositions.

[0085] For any next gen composition described herein, liposomes or liposomal like particles may be micellar or small vesicles. In some embodiments, liposomes or liposomal like particles are small vesicles or vesicle-like, often 100 nm or less, as such sizes may be utilized to extend length of time as an antimicrobial agent and reduce clearance rate when provided as a formulation and / or medicament to a subject. In one or more embodiments, liposomes or liposomal like particles may be nanoparticles and / or nano-sized aggregates thereof, and / or form layers thereof. Neither particles, liposomes or liposomal like particles described herein will contain an additional surfactant. Because the particles, liposomes or liposomal like particles described herein may be caused to form liposomes or liposomal like particles without an additional coupling reaction, this eliminates processing time that is often associated with other / alternative liposomes, and provides an added cost savings. And because the particles, liposomes or liposomal like particles described herein successfully recognize pathogenic microbes as further described elsewhere herein, there is no need to further conjugate the formed particles, liposomes or liposomal like particles described herein with another functional group, such as a protein, antibody, antibody fragment, or carbohydrate, as examples. The next gen compositions described herein, when formed as particles, liposomes or liposomal like particles do not require further modifications to their surface because these next gen compositions are able to recognize and disrupt pathogenic microbes without further functionalization steps.

[0086] Any next gen composition described herein may be isotopically-labeled, such that the next gen composition is structurally the same (isomer or tautomer thereof) but for one or more atoms beingreplaced by an isotope. Representative isotopes include isotopes of hydrogen ( 2 H, 3 H), carbon ( 13 C, 14 C), nitrogen (15N), oxygen (180,17O), phosphorous (31P,32P), fluorine (18F), copper (64Cu or67Cu), iodine (124l or123l or131l), technetium (99mTc), gallium (68Ga or67Ga), indium (113mln orluln), zirconium (89Zr), lutetium (177LU), yttrium (90Y), rhenium (188Re), and chlorine (36CI). One or more next gen compositions and pharmaceutically acceptable salts thereof containing isotopes may have radioactive isotopes, which are useful for host or subject tissue distribution assessments, substrate / pathogen analyses, and other biologic assays. Heavier isotopes (e.g.,2H) may offer greater metabolic stability, such as an increase in in vivo half-life or a reduced dosage requirement. Isotopic labeling will be prepared utilizing well known or referenced procedures readily available and known by one of skill in the relevant art, which includes substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. In addition, or as alternative, liposomes or liposomal like particles or small vesicles herein can be labeled with one or more radioisotopes utilizing known radiolabeling methods available in the field for passive loading (incubating during formation of liposomes or liposomal like particles or small vesicles) or postloading.

[0087] The emulsifier when contained in a next gen composition described herein may be one or more of an emulsifier, stabilizer, gelling agent or thickener, including ones permitted in pharmaceuticals and / or food. Examples include but are not limited to lecithin, fat soluble vitamins, amino acids, cetostearyl alcohol, carrageenan, guar gum, xanthum gum, polysorbate, mono- and diglycerides of fatty acids, sucrose esters, sucroglycerides, polyglycerol esters of fatty acids, polyglycerol polyricinoleate, stearoyl lactylates, and sorbitan esters. A natural emulsifier derived from either a vegetable source (such as acacia, tragacanth, alginates, Chondrus, xanthan, and pectin) or an animal source (such as gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin) are useful as these materials may form hydrophilic colloids when added to water. The emulsifier may also be a finely dispersed solid (dispersed to a sufficiently fine powder) that form particulate films around a dispersed droplet (such as colloidal clays, bentonite, veegum / magnesium aluminum silicate).

[0088] The lipid contained in a next gen composition described herein may be lecithin. The lecithin may be a concentrated lecithin (e.g. L-a-lecithin). The lipid may be phosphatidylcholine (PC) mixed with other phosphatides, in which PC makes up to 25% of the mixture, or PC may make up to 40% of the mixture. The lipid may be a combination of lecithin components, which are naturally occurring components that include glycerophospholipids (e.g., phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylserine (PS) as representative examples), lysophospholipids (e.g., lyso-phosphatidylethanolamine (LPE), sphingomyelin (SPM) as representative examples), bulky fatty acids or sterols (such as cholesterol, choline, choline esters, lipids or fatty acids having a chain length predominantly from about C-14 to C-20), triglycerides, and carbohydrates. In some embodiments, the lipid is any combination of at least one or moreglycerophospholi pids, lysophospholipids, bulky fatty acids or sterols, and lipids having a chain length predominantly from about C-14 to C-20. The lipid may be a mixture of naturally occurring glycerophospholipids. In some embodiments, the lipid is predominantly PC or PC is 25% or greater in a mixture. In some embodiments, the lipid is PC with lecithin components (acetone insoluble phosphatides). The lipid may be from an animal or plant source. The lipid or lecithin may be from a natural source, such as egg, soybean, sunflower, canola, corn, wheat germ, as examples.

[0089] The emulsifier and / or lipid in a next gen composition described herein is in an amount between about 0.01 wt.% and about 50 wt.% or in any amount or range there between (based on total weight of composition in suspension) and as described earlier in the Summary.

[0090] Next gen composition may be provided in a medicament and / or in a formulation (in a form including but not limited to solution, suspension, aerosol, mixture, solid, semi-solid, granules, and others known in the relevant art. For the medicament or formulation, all components will be pharmaceutical grade that can be internalized by a host or subject. The next gen compositions when so formulated may be provided for pharmacology use and / or for medical use.

[0091] In one or more embodiments, the next gen composition will comprise liposomes or liposomal like particles and / or aggregates thereof in a suspension solution, in which the liposomes or liposomal like particles and / or aggregates thereof contain at least one AFAC as described elsewhere herein in an amount that is up to about 10 wt.%, or up to about 5 wt.%, or up to about 1 wt.%, or up to about 0.1 wt.%, based on total wet weight of the next gen composition. The next gen composition comprising liposomes or liposomal like particles and / or aggregates thereof will further contain at least one emulsifier and / or lipid as described elsewhere herein in an amount that is up to about 10 wt.% (or in any amount or range there between), or up to about 5 wt.% (or in any amount or range there between), or up to about 1 wt.% (or in any amount or range there between), or up to about 0.1 wt.% (or in any amount or range there between), based on total wet weight of the next gen composition. In some embodiments, the next gen composition comprising liposomes or liposomal like particles and / or aggregates thereof will also contain at least one biopolymer as described elsewhere herein in an amount that is up to about 10 wt.%, or up to about 5 wt.%, or up to about 1 wt.%, or up to about 0.1 wt.%, based on total wet weight of the next gen composition. The suspension solution will be in an amount between about 50 wt.% and about 99.9 wt.% of the compositions or in any amount or range there between (based on wet weight of the composition).

[0092] For a next gen composition described herein, the biopolymer is a non-toxic biopolymer. The biopolymer may be a copolymer. The biopolymer is often a saccharide or a polysaccharide or a derivative thereof, or a mixture thereof. The biopolymer may be any one or more of chitosan, cellulose (which, e.g., may be a hydroxypropyl methylcellulose), carrageenan, alginate, guar gum, polylysine (which may be poly(L)lysine,poly(L-glutamic acid), poly(hyroxyethyl-l-asparagine, xanthum gum, gellan gum, FucoPol (amixture of monosaccharides, L-fucose, galactose, glucose and glucuronic acid), starch, pectin (which, e.g., may be a low methoxyl pectin), and pullulan. The biopolymer may be deacetylated (e.g., deacetylated chitosan, generally having a degree of deacetylation greater than 60%). The biopolymer may have been previously modified and provided in a form in which the biopolymer has one or more glycol / ethylene glycol groups, hydroxyl groups, carboxyl groups, phosphate groups, sulfur esters, and / or ester groups.

[0093] The biopolymer in a next gen composition described herein is in an amount between about 0.01 wt.% and about 45 wt.% or in any amount or range there between (based on total weight of composition in suspension) and as described earlier in the Summary.

[0094] For next gen compositions described herein, an AFAC is slightly miscible in water. It is initially suspended by mixing or vigorously stirring in water (at a neutral pH), or in a very mild organic acid buffer (such as acetic acid, at a pH less than 7 and generally no lower than pH 6, or in some embodiments, not lower than pH 5). The suspended AFAC is then combined with an emulsifier and / or lipid, which requires mixing by vigorously stirring, which may be under agitating conditions, and / or with sonication. The mixing or stirring may occur for at least an hour or for several hours (up to about 18 hours, or up to about 20 hours, or up to about 22 hours or up to about 24 hours), which causes liposomes or liposomal like particles or vesicles. In one embodiment, when a biopolymer is included, the biopolymer is combined under mixing conditions by vigorously stirring and mixing into the suspension of the AFAC and emulsifier and / or lipid after the AFAC and emulsifier and / or lipid have been mixed and vigorously stirred for at least an hour or for several hours (up to about 18 hours, or up to about 20 hours, or up to about 22 hours or up to about 24 hours). The vigorous stirring and mixing of the biopolymer into the suspension of the AFAC and emulsifier and / or lipid will then continue for at least an hour or for several hours (up to about 18 hours, or up to about 20 hours, or up to about 22 hours or up to about 24 hours). In another embodiment, the biopolymer may be included at the same time or shortly after adding the emulsifier and / or lipid with the AFAC under mixing conditions by vigorous stirring all components for at least an hour or for several hours (up to about 18 hours, or up to about 20 hours, or up to about 22 hours or up to about 24 hours). All components when combined are combined while stirring, which may be vigorous stirring and / or under agitating conditions, and may or may not include sonication, causing liposomes or liposomal like particles or vesicles to form.

[0095] In one or more embodiments, more than one emulsifier and / or lipid may be combined with one or more AFACs. In one or more embodiments, more than one biopolymer may be combined with the one or more AFACs and the one or more emulsifiers and / or lipids. After combining and vigorously stirring to cause liposomes or liposomal like particles or vesicles to form, collection of a final suspended combination may include a filtering step with or without a sterilization step. In some embodiments, filtering and sterilization occur at a same time. Sterilization may include known and methods in the art, such as steam heating (autoclaving), ultraviolet or gamma ionizing irradiation, chemicals, and filtration.Filtration is often considered less destabilizing on liposomes or liposomal like particles or vesicles. Safe storage of such next gen compositions occurs preferably when kept in suspension at or near a neutral pH, under refrigeration, and protected from continued exposure to sunlight or ultraviolet light. In some embodiments, the next gen compositions may be kept under inert gas (e.g., nitrogen or argon) to minimize oxidation (lipid peroxidation). While next gen compositions may be lyophilized before storage, the AFAC alone or in combination with the other components disclosed herein appear to prevent drying, and, when lyophilized may instead form one or more sticky aggregates.

[0096] For a next gen composition described herein, it is not necessary to initially suspend the AFAC in a solvent. Thus, there is also no need to remove or evaporate the solvent. Should it be desired to initially suspend the AFAC in a solvent, which is not required, the solvent may be a more neutral solvent (not highly polar and not non-polar). Representative examples include, but are not limited to benzene, toluene, ether solvents, diethylether, diisopropylether, dimethoxyethane, chloroform, dichloromethane, dichloroethane, tetrahydrofuran, dichloroethane, acetone, dioxane, ethylacetate, ethylene glycol, dimethyl acetate, dimethylsulfoxide, dimethylformamide, aniline, diethylamine, nitromethane, acetonitrile, and pyridine, and n-methylpyrrolidinone. Safer solvents include, but are not limited to: 2- methyl tetrahydrofuran, acetic acid, acetonitrile, cyclohexane, dimethyl sulfoxide, heptane, isooctane, methyl t-butyl ether, methylcyclohexane, tetrahydrofuran, toluene, xylenes. The solvent if utilized, is evaporated and removed before additional steps are performed for forming the next gen composition.

[0097] For a next gen composition described herein, it is not necessary to suspend the AFAC in a buffer solution or a mild acidic buffer solution. The AFAC, which has some miscibility in water, may be and is often preferably suspended in water. In addition, the one or more emulsifier / lipid may also be suspended in water before mixing and stirring with the suspended AFAC. Similarly, the one or more biopolymer may also be suspended in water before mixing and stirring with the suspended AFAC and the one or more emulsifier / lipid. Should a buffer solution be desired, which is not required, suitable and representative buffer solutions include, but are not limited to, sodium acetate-acetic acid buffer, citric acid-sodium citrate buffer, citric acid-disodium phosphate buffer, disodium phosphate-monosodium phosphate buffer, imidazole (glyoxaline)-hydrochloric acid buffer, sodium carbonate-sodium bicarbonate buffer, and phosphate buffer. The buffer solution may have a neutral or near neutral pH, or may be mildly acidic, and generally not less than pH 6. In some embodiments, the buffer solution may be mildly acidic and not less than pH 5. In some embodiments, the buffer solution is not less than pH 5.

[0098] Next gen compositions described herein, when prepared, have been found to be stable at a mildly acidic pH and a neutral pH and a basic pH (data not shown). For internal use, a next gen composition in a pharmaceutically acceptable or medically acceptable suspension or aerosol, for example, may be pH adjusted according to the target microbial pathogen and / or the pH of its environment or location in a host or subject. While a stomach or portions of a Gl tract may have a pH aslow as 1 or 2, vaginal epithelium may have a pH of or between about 3.5 to about 4.5, and the colon may have a pH between about 5 or about 6, while skin wounds may have a more neutral pH or a basic pH that can be as high as pH 10 (associated with infections by certain skin and soft tissue bacteria).

[0099] While next gen compositions prepared with an AFAC as described herein are not expected to have broad-spectrum antimicrobial activity, the findings as disclosed below show that such compositions, when caused to form liposomes or liposomal like particles or vesicles, do have broadspectrum antimicrobial activity against pathogenic bacteria and pathogenic fungus or fungi.

[0100] The findings disclosed herein contradict prior reports that are based on structural assessments of the AFACs. For example, according to a structural assessment of BOA and of LO, there is no likelihood that structures (I) or (II), or any tautomeric form of structure (I) or (II) would exhibit broadspectrum antimicrobial activity. (See., e.g., MF Richter, et al., "Predictive compound accumulation rules yield a broad-spectrum antibiotic," 2017 Nature Vol. 545, pp 299-304). In brief, a structural assessment is used to predict a probability or likelihood that a molecule will be capable of accumulating in bacteria, which is necessary for antimicrobial activity against at least Gram-negative bacterial species. Assessment properties were identified utilizing an online classification program referred to as eNTRyway, which is found at www.entry-way.org. According to the assessments, neither structure (I) nor structure (II) have a primary amine, and both have high flexibility (high number of rotatable bonds, not including N-C bonds), which, together, correlates with negligible accumulation, and hence, little to no probability that either structure will exhibit sufficient antimicrobial activity against Gram-negative bacteria or be suitable as a therapeutic agent against Gram-negative bacteria in a subject (having an infection cause by Gramnegative bacteria). A summary of findings is depicted in TABLE I, utilizing Ampicillin as a comparator, which is a successful therapeutic agent and is utilized against Gram-negative bacteria in medical and hospital settings to treat subjects having an infection caused by (or suspected of being caused by) Gramnegative bacteria.

[0101] Unexpectedly, and contrary to the structural assessment and prediction identified above, each next gen composition described herein, when caused to form liposomes or liposomal like particles or vesicles and tested against a variety of microbial pathogens, was found to exhibit antimicrobial activity against Gram-negative bacteria, as well as Gram-positive bacteria and various fungus or fungi. BOA and LO when caused to form liposomes or liposomal like particles or vesicles as described herein were foundin such forms to inhibit growth of a plurality of Gram-positive bacteria, including various strains of Staphylococcus (e.g., S. aureus group, S. epidermidis group various strains of Streptococcus (e.g., Group A Streptococcus, Group B Streptococcus, S. pneumoniae group, S. pyogenes group, S. anginosus group BOA and LO when caused to form liposomes or liposomal like particles or vesicles were found in such forms to inhibit growth of a plurality of Gram-negative bacteria, including various strains of Enterobacteriaceae spp. (Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Proteus mirabilis, Proteus vulgaris, Klebsiella pneumonia, Morganella morganii, Serratia marcescens), and Acinetobacter baumannii, Pseudomonas aeruginosa, Salmonella enteritidis, Salmonella enterica, Shigella dysenteriae, as well as various strains of fungi (Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (e.g., fungi causing mucormycosis or mycetoma) (not all data shown). Some bacterial strains that were tested were drugresistant strains, resistant to one or more current anti-infectives (e.g., S. aureus, E. coli, K pneumonia, Salmonella enterica).

[0102] Without being bound by theory, the AFAC having a 12 carbon backbone may be in part responsible for the unexpectedly findings that such AFACs when caused to form liposomes or liposomal like particles or vesicles with an emulsifier and / or lipids, with or without a biopolymer, have antimicrobial activity against a plurality of pathogenic bacteria and a plurality of pathogenic fungus or fungi by inhibiting growth of the plurality of pathogenic bacteria and the plurality of pathogenic fungus or fungi. The unexpected findings were not predicted in view of prior literature reports. The unexpected findings were also not predicted in view of the assessment of the chemical structures of structure (I) and structure (II). Nonetheless, in based on cumulative data and MIC calculations from in vitro testing against a plurality of pathogenic bacteria and a plurality of pathogenic fungus or fungi, the data provides evidence that a next gen composition described herein may be formulated for internal delivery and will be sufficient and / or effective as a medicament or for medical therapy for a subject having or suspected of having at least one microbial pathogen (or a spectrum of pathogens) or an infection caused or suspected of being caused by at least one microbial pathogen (or a spectrum of pathogens). The data also provides support that one or more next gen compositions described herein may be utilized for empirical therapy and / or for targeted therapy (in which inclusion of microbiologic susceptibility testing of aerobically growing bacteria and the results may be utilized to provide value of therapy decision).

[0103] A mean inhibitory concentration (MIC) for each next gen composition against a plurality of microbial pathogens was evaluated from pathogen tests to assess in vitro levels of susceptibility or resistance of a specific bacterial strain to each next gen composition when caused to form liposomes or liposomal like particles or vesicles. MIC values were determined utilizing a standardized broth microdilution method in accordance with the National Committee for Clinical Laboratory Standards(NCCLS) guidelines. NCCLS guidelines are in concert with guidelines established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST), which represents guidance formed by the European Society of Clinical Microbiology and Infectious Diseases. In brief, a microbial pathogen suspension was adjusted to a 0.5 McFarland standard to yield a final inoculum of about 5xl05colonyforming units (CFU) / mL (density being between 3xl05and 7xl05CFU / mL). Inoculum density was controlled by measuring using a densitometer. Dilutions of each next gen composition caused to form liposomes or liposomal like particles or vesicles in suspension, and of inocula were made in sterile, cation adjusted Mueller-Hinton broth media. Any supplementation of the broth media was dependent on the bacteria being tested, as outlined in the guidelines. An inoculum volume of 100 pl was added to each well of a standard microdilution tray, in which each well also containing 100 pl of broth and one dilution (from a series of dilutions) of one next gen composition caused to form liposomes or liposomal like particles or vesicles in suspension; serial dilutions of each composition were 2-fold serial dilutions. All inoculated microdilution trays were incubated at 35° Centigrade, in ambient air (aerobic conditions), for approximately 20-24 hours. Following incubation, the lowest concentration of a next gen composition that prevented visible growth was recorded as the MIC. The microdilution method was repeated at least 3 times for each pathogen tested and for each composition tested.

[0104] Next gen compositions were prepared by suspending while vigorously stirring for up to 24 hours in total, in which an AFAC, BOA or LO, was added to sterilized water at room temperature. The amount of BOA or LO can be 10 mg per 1 liter of water, or more, up to saturation. While continuing to stir vigorously, a lipid / emulsifier was added. In this example, lecithin was added to the suspension as L- a-lecithin from soybean containing >94% phosphatidylcholine and <2% triglycerides (Sigma Aldrich 429415), and the suspension was stirred for another hour or more at room temperature. The suspension contained 20 mg / liter of BOA or LO, and 22 g / liter of lecithin. Here, sterilized water (at a neutral pH) was utilized. It is understood that the AFAC and / or lecithin (as the emulsifier / lipid) may be suspended in a buffer solution, such as a mildly acidic organic acid, having a pH less than 7 and not less than 6 or not less than 5. It is also understood that mixing may include sonicating. The suspension is vigorously stirred for one to several hours and up to 18 hours or up to 20 hours or up to 24 hours. In a first collection, the vigorous stirring and mixing caused liposomes or liposomal like particles or vesicles and aggregates thereof to form, which were collected by filtration with a sterile filter (e.g., a micropore or nanopore sterile filter), which caused liposomes or liposomal like particles or vesicles and few aggregates thereof to be collected. Any filter size may be utilized to control the size of the collection. For example, utilizing a 0.45 micrometer sterilized filter causes a collection of liposomes or liposomal like particles or vesicles that are less than 0.45 micrometers in diameter. A finer filter or finer filtration system (e.g., ultrafiltration, reverse osmosis) will cause a collection having on average a smaller cross-sectional diameter.

[0105] In some embodiments, next gen compositions were not collected after combining the AFAC and the emulsifier / lipid. Instead, to the vigorously stirred suspension containing the AFAC (e.g., BOA or LO), a biopolymer was slowly added, which, in this example was either chitosan or, in a separate batch, was glycol chitosan. The chitosan and the glycol chitosan were each initially suspended independently in sterilized water (about 15 grams to 1 liter), then 1 part chitosan was added to the stirring suspension, such that the final amount of chitosan (or glycol chitosan) was about 7.5 g per liter. The final amount of BOA or LO was about 10 mg / liter and the amount of lecithin was about 11 g / liter. The suspension was then vigorously stirred for one to several hours and up to 18 hours or up to 20 hours or up to 22 hours or up to 24 hours. The vigorous stirring and mixing caused liposomes or liposomal like particles or vesicles and aggregates thereof to form, which were collected in a second collection by filtration with a sterile filter (e.g., a micropore or nanopore sterile filter), which caused liposomes or liposomal like particles or vesicles and few aggregates thereof to be collected. Any filter size may be utilized to control the size of the collection. For example, utilizing a 0.1 micrometer sterilized filter causes a collection of particles that are less than 0.1 micrometers in diameter. A finer filter or finer filtration system (e.g., ultrafiltration, reverse osmosis) will cause a collection having on average a smaller cross-sectional diameter.

[0106] Collections (first collection or second collection) for pharmaceutical use may be maintained and / or stored in a suspension solution and utilized directly, or may be prepared to be more concentrated, and then reconstituted or re-suspended in a suspension solution, which may be water (e.g., sterile and / or distilled and / or pure water), which is most cost effective and may be preferred for that reason, or in an isotonic solution (e.g., normal saline solution, dextrose solution, Ringer's solution, lactated Ringer's solution) for utilization in a formulation and / or as a medicament. A hypotonic solution (e.g., hypotonic saline solution, hypotonic dextrose solution) or a hypertonic solution (e.g., hypertonic saline solution, hypertonic dextrose solution) or a phosphate buffered saline solution may be utilized but may negatively affect stability.

[0107] Collections as described above provide next gen compositions that may be formulated as a medicament for medical therapy or clinical therapy. Collections are generally in the form of particles and / or aggregates of particles, and may include layers of aggregates of particles. The particles are liposomes or liposomal like particles or small vesicles. Collections may be manipulated to form of a film or sheet, or a plurality of small nano-sized or micro-sized layers or sheets, utilizing methods known in the art. Collections may have a charge, particularly when a positively charged biopolymer or negatively charged biopolymer is utilized. For example, glycol chitosan will provide a positive charge to surfaces of the liposomes or liposomal like particles or small vesicles and / or aggregates thereof. However, it is noted that with the AFACs described herein, a neutral biopolymer is sufficient and effective for yielding broadspectrum antimicrobial activity of a collection containing an AFAC as described herein. This was not anticipated, as prior reports have suggested that other lauric acid derivative require a chargedenvironment or utilization of a positively charged biopolymer in order to be active against Gram-negative bacteria. Here, when utilizing AFAC under the conditions described herein, the AFAC did not require a charged environment or utilization of a positively charged biopolymer, thus such conditions were not necessary and don't have to be included.

[0108] In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC (e.g., BOA and / or LO) to lipid / emulsifier ratio (e.g., lecithin or PC or mixtures thereof) was in a ratio of about 0.001 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC to lipid / emulsifier was in a ratio of about 0.0009 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC to lipid / emulsifier was in a ratio of about 0.01 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC to lipid / emulsifier was in a ratio of about 0.05 to about 1, respectively. When making liposomal compositions and / or liposomal like composition, the AFAC to lipid / emulsifier ratio may be between about 0.001 to 0.5 and about 0.75 to 1.25, respectively.

[0109] In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC (e.g., BOA and / or LO) to biopolymer ratio (e.g., chitosan, glycol chitosan, cellulose, alginate, pectin) was in a ratio of about 0.001 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC to biopolymer was in a ratio of about 0.01 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, AFAC to biopolymer was in a ratio of about 0.05 to about 1, respectively. When making liposomal compositions and / or liposomal like composition, the AFAC to lipid / emulsifier ratio may be between about 0.001 to 0.5 and about 0.75 to 1.5, respectively.

[0110] In some embodiments, when making liposomal compositions and / or liposomal like composition, lipid / emulsifier (e.g., lecithin or PC or mixtures thereof) to biopolymer ratio (e.g., chitosan, glycol chitosan, cellulose, alginate, pectin) was in a ratio of about 0.6 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, lipid / emulsifier to biopolymer was in a ratio of about 0.5 to about 1, respectively. In some embodiments, when making liposomal compositions and / or liposomal like composition, lipid / emulsifier to biopolymer was in a ratio of about 1 to about 1, respectively. When making liposomal compositions and / or liposomal like composition, lipid / emulsifier to biopolymer ratio may be between about 0.5 to 1 and about 1 to 1.2, respectively.

[0111] In a combination of AFAC (e.g., BOA and / or LO) and emulsifier and / or lipid, with or without a biopolymer, the emulsifier and / or lipid (e.g., lecithin, PC or combinations thereof) may be added in an amount or quantity so that it makes up about 0.01% up to about 50% of the solutes / solids in the suspension.

[0112] In a combination of AFAC (e.g., BOA and / or LO) and emulsifier and / or lipid and a biopolymer, the biopolymer (e.g., chitosan or cellulose or alginate or pectin, etc.) may be added in an amount or quantity so that it makes up about 0.01% to about 45% of the solutes / solids in the suspension.

[0113] In some embodiments, a final ratio was about 1 part BOA or LO suspension (~10 mg / L) to about 9 parts of a 2.2% lipid / emulsifier suspension to about 10 parts of a 1.5% biopolymer suspension.

[0114] Collections of next gen compositions caused to form liposomes or liposomal like particles or small vesicles as described herein may be formulated into pharmaceutical compositions that comprise a sufficient amount and / or a therapeutically effective amount and / or inhibitory amount and / or antimicrobially effective amount of at least AFAC and at least one emulsifier and / or lipid, with or without at least one biopolymer. The pharmaceutical compositions may be provided as a medicament or for medical or clinical therapy to a host or subject in need thereof. Such collections due to their antimicrobial action, having growth inhibitory activity against a plurality of microbial pathogens, may be utilized for at least any one or more of the following: (a) delivering to a cell; (b) delivering to a microbial pathogen; (c) providing to an outer membrane of a target cell; (d) providing to an outer membrane of a microbial pathogen; (e) providing to a host or subject; (f) for use in medical therapy (e.g., for a host or subject having or suspected of having a microbial infection); (g) for therapeutic use or medical use in a therapeutically effective amount; (g) for therapeutic use or medical use in a sufficient amount considered acceptable or suitable for antimicrobial activity; (h) for broad-spectrum antimicrobial activity against a pathogenic Gram-positive bacteria and a pathogenic Gram-negative bacteria (any one or more of which may or may not be resistant to alternative anti-infective agents); (i) for broad-spectrum antimicrobial activity against a plurality of pathogenic microorganisms (pathogenic Gram-positive bacteria, pathogenic Gram-negative bacteria, and / or pathogenic fungus of fungi, any one or more of which may or may not be resistant to alternative anti-infective agents); (j) for broad-spectrum antimicrobial activity against a pathogenic Gram-positive bacteria and a pathogenic fungus (any one or more of which may or may not be resistant to alternative anti-infective agents); (k) for broad-spectrum antimicrobial activity against a pathogenic Gram-negative bacteria and a pathogenic fungus (any one or more of which may or may not be resistant to alternative anti-infective agents); (I) for broad-spectrum antimicrobial activity against a pathogenic Gram-negative bacteria, a pathogenic Gram-positive bacteria, and a pathogenic fungus (any one or more of which may or may not be resistant to alternative anti-infective agents); (m) for use or therapeutic use as a medicament; (n) administering an inhibitory amount of a next gen pharmaceutical composition to one or more of a Gram-negative bacteria and / or fungus or fungi; (o) inhibiting growth of a Gram-negative bacteria upon or after delivery to a subject or host; (p) modulating virulence of a Gramnegative bacterial infection upon or after delivery; (q) inhibiting growth of a Gram-positive bacteria upon or after delivery to a subject or host; (r) modulating virulence of a Gram-positive bacterial infection upon or after delivery; (s) inhibiting growth of a fungus or fungi upon or after delivery to a subject or host; (t)modulating virulence of a fungus or fungi upon or after delivery; (u) providing in a kit for medical use or therapeutic use; (v) for tissue distribution assessments, substrate / pathogen analyses, and other host or subject biologic assays when utilizing one or more isotopically labeled next gen pharmaceutical compositions.

[0115] For purposes herein, growth inhibition or growth inhibitory activity is reducing the rate of increase in numbers of a population of a particular microbial pathogen (bacteria and / or fungus). In some embodiments, population of a particular microbial pathogen may increase but at a reduced rate. In some embodiments, growth of the population is stopped. In some embodiments, the numbers of a particular microbial pathogen in the population are reduced. In some embodiments, the population of a particular pathogen is eliminated. Without being bound by theory, activity is believed to involve some interaction with microbial pathogen membranes, possibly largely through an initial association between the pathogen membrane and the emulsifier and / or lipid, orthe emulsifier and / or lipid and biopolymer, when a biopolymer is present, in which the association is believed to decrease membrane fluidity and / or disrupt normal membrane function of the microbial pathogen by interfering with at least a portion of its outer membrane.

[0116] The broad-spectrum growth inhibitory activity of collections of next gen compositions caused to form liposomes or liposomal like particles or small vesicles as described herein was not anticipated from prior published reports. Moreover, structural components and / or configurations that predict growth inhibitory activity against Gram-negative bacteria are not found in BOA or in LO. It is further noted that antimicrobial activity of BOA or LO when utilized independently and alone (and not as described herein) have little to no antimicrobial activity against microbial pathogens.

[0117] Efficacy of collections of next gen compositions caused to form liposomes or liposomal like particles or small vesicles and / or aggregates thereof as described herein (which includes next gen pharmaceutical compositions) is dependent on at least the AFAC described herein and on formation of liposomes or liposomal like particles or small vesicles as described herein and / or aggregates thereof (which may or may not form one or more layers or pseudo layers).

[0118] Any collection of next gen compositions caused to form liposomes or liposomal like particles or small vesicles as described herein may be further formulated into a pharmaceutical composition with addition of one or more pharmaceutically acceptable carriers and / or excipients. The one or more pharmaceutically acceptable carriers or excipients are generally non-toxic, inert, solid, semi-solid or liquid, and are selected based on at least a compositional form and desired mode of delivery. Acceptable excipients include but are not limited to solutions, sugars (e.g., lactose, glucose, sucrose, mannitol); starches (e.g., corn starch, potato starch); cellulose (e.g., sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate); powdered tragacanth; malt; cocoa butter; suppository waxes; paraffin; oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, coconut oil, soybean oil); glycols(e.g., propylene glycol); fatty acid ester (e.g., ethyl oleate, ethyl laurate); agar; buffering agents (e.g., magnesium hydroxide, aluminum hydroxide); absorbents (e.g., kaolin, bentonite clay); pyrogen-free water; ethyl alcohol; phosphate buffered solutions; binders (e.g., carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia); humectants (e.g., glycerol); disintegrating agents (e.g., agar-agar, calcium carbonate, potato starch, tapioca starch, alginic acid, certain silicates, sodium carbonate); non-toxic compatible lubricants (e.g., talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, magnesium stearate), releasing agents, preservatives, and coating agents. When desired a coloring agent, sweetener, flavoring, and / or antioxidant may be provided, which may be useful or desired for certain modes of delivery. The solutions may be any acceptable solutions for drug administration, including but not limited to water (e.g., sterile and / or distilled and / or pure water) or in an isotonic solution (e.g., normal saline solution, dextrose solution, Ringer's solution, lactated Ringer's solution) or a hypotonic solution (e.g., hypotonic saline solution, hypotonic dextrose solution) or a hypertonic solution (e.g., hypertonic saline solution, hypertonic dextrose solution) or a phosphate buffered saline solution.

[0119] When formed as a pharmaceutical composition, said pharmaceutical composition may be administered to a host or subject (human, animal) by a desired mode of delivery, in which the mode of delivery may be orally, rectally, parenterally, intracisternally, intravaginally, intramuscularly, intraperitoneally, topically, bucally, nasally, or by enema. A composition herein may be provided in one or in a variety of different forms, including but not limited to suspension, tablet, capsule, pill, granules, emulsion / microemulsion, inhalant, drop, syrup, spray, gel / ointment / paste / cream, aerosol, resinate, waxinate, and suppository.

[0120] When formulated into a pharmaceutical composition for inhalation, aerosol formulations may be nebulized predominantly into particle sizes that can be delivered to the terminal and respiratory bronchioles since certain pathogenic bacteria may be throughout the airway to bronchi, bronchiole and lung parenchyma, as well as terminal and respiratory bronchioles. Delivery of an aerosolized formulation may include an aerosol forming device (e.g., jet, vibrating porous plate, ultrasonic nebulizer, energized dry powder inhaler) that allows formation of aerosol particles, such as particles having an average (mass median) diameter between about 1 and about 5 pm. An aerosolized formulation preferably has balanced osmolarity ionic strength and chloride concentration, and the smallest aerosolizable volume that is able to deliver a sufficient dose or an effective dose or an inhibitory dose or a modulatory dose of the next gen pharmaceutical composition to the pathogen.

[0121] Delivery of a next gen pharmaceutical composition as described herein to a host or subject provides a novel therapeutic option against one or more pathogenic microbes (e.g., Gram-positive pathogenic bacteria, Gram-negative pathogenic bacteria, fungus or fungi, any of which may or may not be resistant to at least one current anti-infective). With delivery of a next gen pharmaceuticalcomposition to a host or subject, a novel medicament having broad-spectrum antimicrobial activity against a plurality of pathogenic microbes (Gram-positive pathogenic bacteria, Gram-negative pathogenic bacteria, fungus or fungi, any of which may or may not be resistant to at least one current anti-infective) is provided to the host or subject, the medicament being for therapeutic use against the pathogenic microbes or for treatment of an infection caused by or suspected of being caused by the pathogenic microbes, or for prevention of an infection caused by or suspected of being caused by the pathogenic microbes.

[0122] In some embodiments, delivery of a next gen pharmaceutical composition will include providing at least a sufficient amount of the next gen pharmaceutical composition to a host or subject for antimicrobial activity against one or more pathogenic microbes. In some embodiments, delivery of a next gen pharmaceutical composition will include delivering at least a therapeutically effective amount or an inhibitory amount to a host or subject for antimicrobial activity against one or more pathogenic microbes. As is understood by a person of skill in the relevant art, a therapeutically effective amount or an inhibitory amount for any particular host or subject will depend upon many factors, such as the weight of the host or subject, the severity of infection, route of administration, as examples of factors well known in the medical arts.

[0123] In some embodiments, a dose of a next gen pharmaceutical composition can be in an amount in which the collection caused to form liposomes or liposomal like particles or small vesicles and provided in a dose as a next gen pharmaceutical composition exceeds the MIC for a clinically tested strain. It is anticipated that dosing will be at least twice daily. Dosing may be continuous and / or on a timer. Daily, a dosing may be up to or greater than 200 mg (the weight comprising at least a collection caused to form liposomes or liposomal like particles or small vesicles) / kg body weight / day. In general, a representative therapy with a next gen pharmaceutical composition described herein will include delivery to a patient in need of such therapy, the delivery providing from about 1 mg to about 12 g of an AFAC and / or BOA and / or LO daily.

[0124] When a kit is provided with a next gen pharmaceutical composition described herein, the kit may include one container or a plurality of containers or divided containers for containing the next gen pharmaceutical composition. The container may be a holder or receptacle or vessel or pouch, as examples, provided in a suitable material, such as paper, cardboard, glass, plastic, or other acceptable material, depending on the form of the composition, which is understood by one of skill in this art. The container may be in a variety of shapes, represented by box, bottle, jar, bag or resealable bag, blister pack, vial, as examples. More than one container may be provided in a single kit (e.g., tablets contained in a bottle that is contained in a box). The kit may further include a suspending solution and will include information and / or instructions, such as for delivery, dosing, and / or as a written memory aid or reminder. The kit may further include a dispenser for dosing.

[0125] Collections of next gen compositions containing either BOA or LO, in which the collections included either BOA or LO with an emulsifier and / or lipid (lecithin) and a biopolymer (chitosan or glycol chitosan) and caused to form liposomes or liposomal like particles or small vesicles and / or aggregates thereof as described elsewhere herein, were tested against microbial pathogens for pathogen susceptibility. Microbial pathogens included Gram-positive bacteria (various strains of S. aureus, S. epidermidis, S. pneumoniae, C. difficile, Group A Streptococcus, Group B Streptococcus, including drug resistant strains) and Gram-negative bacteria (E. coli, Enterobacter cloacae, Enterobacter aerogenes, Haemophilus influenza, Klebsiella pneumonia, Salmonella enterica, Salmonella enteritidis, Shigella dysenteriae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, including some drug resistant strains) and fungi (various strains of Candida) (not all data shown). Susceptibility testing was performed in vitro, as described elsewhere herein, and all collections of next gen compositions were found to exhibit broad-spectrum growth inhibitory activity against microbial pathogens sufficient for antibacterial utilization.

[0126] For MIC determination against pathogenic bacteria or fungi shown in TABLES 2-5, to a collection of a next gen composition comprising liposomes or liposomal like particles or small vesicles and / or aggregates thereof containing an AFAC that was either BOA or LO, sterile water was added followed by a serial dilution; the minimal dilution was 10 mg / ml. All prepared samples were tested against a pathogen and evaluated for inhibitory activity or antibacterial activity against that pathogen using a broth microdilution susceptibility test as described previously, and utilizing the standardized methodology outlined elsewhere herein, and as is understood by one of skill in the relevant art. Positive control samples utilized ethyl laurate, which were prepared in a same manner as outlined above, with the same serial dilutions.

[0127] For TABLES 2-5, the pathogen testing results and MIC are shown for Escherichia coli, Salmonella enterica Streptococcus pyogenes, Staphylococcus aureus (including MRSA strains), Staphylococcus epidermidis and for fungi, MIC are shown for Candida albicans and Candida auris. Neither BOA nor LO were found to provide acceptable MIC values, ones that would inhibit or prevent growth of the target pathogen (data not shown). Both BOA and LO were, independently, miscible with water, and collections of each (as liposomal compositions and / or liposomal like particles comprising BOA or LO along with a lipid and a biopolymer) were suspended by mixing vigorously in water as further described, and dilution samples were tested utilizing a broth microdilution assay, against each pathogen using collections comprising BOA and collections comprising LO, in which the amounts BOA or LO in the dilution samples varied from about 0.0009 wt.% to about 10 wt.%.

[0128] TABLE 2 shows MIC when testing collections of liposomes or liposomal like particles or vesicles and / or aggregates thereof that contained BOA as the AFAC with lecithin as the emulsifier / lipid, and chitosan as the biopolymer. Comparison data utilizing ethyl laurate (EL) instead of BOA is also shown.When sodium alginate or pectin or cellulose was the biopolymer, the liposomes or liposomal like particles were also effective for inhibiting growth (data not shown).

[0129] TABLE 3 shows MIC when testing collections of liposomes or liposomal like particles or vesicles and / or aggregates thereof contained BOA as the AFAC with lecithin as the emulsifier / lipid and glycol chitosan as the biopolymer. Comparison data utilizing ethyl laurate (EL) instead of BOA is also shown. When sodium alginate or pectin or cellulose was the biopolymer, the liposomes or liposomal like particles were also effective for inhibiting growth (data not shown).

[0130] TABLES 4 shows MIC when testing collections of liposomes or liposomal like particles or vesicles and / or aggregates thereof contained LO as the AFAC with lecithin as the emulsifier and / or lipid, and chitosan as the biopolymer. Comparison data utilizing ethyl laurate (EL) instead of BOA is also shown. When sodium alginate or pectin or cellulose was the biopolymer, the liposomes or liposomal like particles were also effective for inhibiting growth (data not shown).

[0131] TABLE 5 shows MIC when testing collections of liposomes or liposomal like particles or vesicles and / or aggregates thereof contained LO as the AFAC with lecithin as the emulsifier / lipid, and glycol chitosan as the biopolymer. Comparison data utilizing ethyl laurate (EL) instead of BOA is also shown. When sodium alginate or pectin or cellulose was the biopolymer, the liposomes or liposomal like particles were also effective for inhibiting growth (data not shown).

[0132] For TABLES 2-5, liposomal compositions and / or liposomal like particles comprising BOA or LO were formed or caused to be formed by initially suspending the lecithin (the emulsifier and / or lipid) in sterilized water by stirring with a magnetic stirrer until suspended, about 1-3 hours, in which the suspension was a 2.2% lecithin suspension, Here, the emulsifier and / or lipid was provided as a powder, as soybean L-a-phosphatidylcholine >25% or >40% with >95% phosphatides from soybean, see Millipore Sigma No. 44924). It is understood that cholesterol or other sterol may be added to lipid suspension. BOA or LO as a powder form was added to the lecithin suspension by adding and stirring with magnetic stirrer until suspended, about 1-3 hours. BOA was CAS No. 18934-81-1 (e.g., Sigma No. 09780), and LO was CAS No. 1643-20-5 (e.g., Sigma No. 40234). The suspension was then sonicated, to which a suspension of about 1.5% chitosan in sterilized water or about 1.5% glycol chitosan was added. Chitosan and glycol chitosan were each in a deacetylated form. Chitosan was a medium molecular weight, also referred to as deacetylated chitin, or poly(D-glucosamine) (e.g., Sigma No. 448877). It is understood that high molecular weight and low molecular weight chitosan, deacylated, may also be utilized. In at least one embodiment, a ratio was about 0.6 to 0.7 parts lecithin to about 1 part chitosan when combined in the suspension. More AFAC may also be added to saturation. With too much lecithin and / or chitosan, more will remain unincorporated in liposomal compositions and / or liposomal like particles. With addition of chitosan, the combination was blended in a blender (or other vigorous mixing device) for about 1 hour, followed by sonication for up to 1 hour. It is understood that stirring with a magnetic stirrer may also beperformed after blending, for better incorporation, especially when more AFAC is included, and the stirring may take place for up to 24 hours. Of course, it is understood that other amounts and / or ratios are possible and may be prepared within the scope of the description herein elsewhere, and such amounts and / or ratios may be utilized to achieve a next gen composition. After blending (which may or may not be followed by stirring), the suspension was sonicated, followed by a filtering step. Here, samples were sonicated for about 30 minutes and then filtered through a 0.45 micrometer pore size sterile filter. After sonicating and filtering, next gen compositions (containing either BOA or LO) were nano-sized liposomes, or liposomal like particles or small vesicles with few aggregates. Sonication produced smaller particles (generally nanoparticles, and filtering helped reduce aggregation). The next gen compositions were tested after being prepared. A similar procedure was utilized for the positive control in which EL was substituted for BOA or LO.

[0133] The minimum inhibitory concentration (MIC) needed to prevent growth of the target microbial pathogen was evaluated based on a method published by Clinical Laboratory Standards Institute (CLSI), broth microdilution method M-07 (M07). The pathogens tested were clinical isolates, strains isolated from clinical patients, with or without resistance to one or more alternative antibiotics.

[0134] As depicted in TABLES 2-5, next gen compositions as liposomes or liposomal like particles or small vesicles and / or aggregates thereof with BOA or LO, and with an emulsifier and / or lipid and a biopolymer, provided growth inhibitory activity against a broad-spectrum of microbial pathogens, including Gram-positive bacteria, Gram-negative bacteria and fungi. The antimicrobial activity and growth inhibitory activity of next gen compositions containing either BOA or LO did not appear to be substantially dependent on degree of hydrophobicity (or lipophilicity), which is measured as a logarithmic value of the octanol-water partition coefficient P, or log P, since BOA and LO have different log P values. The antimicrobial activity and growth inhibitory activity of next gen compositions containing either BOA and / or LO contradicts findings by others because the broad-spectrum activity disclosed herein, and in particular, activity against Gram-negative bacterial pathogens, did not require a terminal amino group, as has been predicted by others of skill in the field of this invention.

[0135] Re-suspended next gen compositions were also tested on bacterial biofilms. In brief, bacteria, including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenza, and Bacteriodes fragilis, were grown independently in an appropriate liquid, nutrient-containing broth or media, in 96-well plates at 37 degrees Centigrade by leaving on a shaker for about 48 hours, simulating active growing phase of biofilm. Here, the shaker was set at 180 rpm. In wells, bacteria grew and a bacterial biofilm formed, which were either adhered to the edges of a well and / or were on the liquid surface, often on outside edges of a well where plate, liquid and air intersect. Testing was performed with each next gen composition comprising collections of liposomes or liposomal like particles or small vesicles and / or aggregates thereof containing BOA or LO, and with an emulsifier and / or lipid and a biopolymer, which were prepared as described above in dilutions of 1% by weight and decimal dilution thereof in 96-well microtiter plates. A control with a same suspension solution was also utilized. After addition of said collections of liposomes or liposomal like particles or small vesicles and / or aggregates thereof to a well, each 96-well plate was allowed to grow at 37 degrees Centigrade on a shaker set at 180 rpm for about 24 hours. After 24 hours, wells were washed to remove non-adherent cells and the remaining bacterial biofilm in each well were stained at room temperature with a crystal violet stain (which can be with or without a mordant, depending on whether differentiation of Gram-negative and Gram-positive is desired, as is understood to one of ordinary skill in this field). The crystal violet stains cells in the biofilm a purple color. The crystal violet stain solution can be left for a minute or a few minutes or generally no more than 1 hour (depending on maturity of the biofilm). The wells are then washed at least once and up to three times and the adherent biofilm cells in each well are de-colorized (generally with an ethanol solution added in a same amount to each well) in which the crystal violet (which had been absorbed by cells) is solubilized by the de-colorized solution. The de-colorized solution in each wellis preserved by transferring all of the solution in a well to a clean and labeled well in a corresponding clean 96-well plate (each clean well being labeled to correspond with said well from the 96-well plate from which the crystal violet containing de-colorized solution was removed from). Each clean 96-well plate was read by a plate reader or a multi-well plate UV-VIS spectrometer set at an absorbance of 530- 600 nm (generally determined by the filter ability of the instrument used). With such a test, introduction of a collection of liposomes or liposomal like particles or small vesicles and / or aggregates thereof with BOA or LO, and with an emulsifier and / or lipid and a biopolymer to a well (that contained an actively growth bacterial biofilm) resulted in undetectable (no stain) being recorded in the de-colorized solution obtained from that well. The absence of detectable stain was observed when the amount of BOA or LO utilized was anywhere from 1% by weight and down to 0.01% by weight. Each amount was evaluated three or more times. Accordingly, the findings show that a collection of liposomes or liposomal like particles or small vesicles and / or aggregates thereof containing BOA or LO, with an emulsifier and / or lipid and a biopolymer was successful at disturbed a biofilm and / or inhibiting biofilm formation of an adherent biofilm after 24 hours. From the combined testings, next gen compositions herein, in one or more formulations and / or medicaments, will disturb a biofilm or will inhibit biofilm formation as well as inhibit biofilm infection from at least some of the more common biofilm pathogens, including S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

[0136] The AFAC described herein are considered safe and all components in next gen compositions described herein will have GRAS status in the U.S. and a complementary or good safety status outside the U.S.

[0137] Although representative processes and compositions have been described in detail herein, those skilled in the art will recognize that various substitutions and modifications for preparation of the new lauric acid derivatives may be made without departing from the scope and spirit of what is described and defined by the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A liposomal composition comprising: an active constituent that contains 12 carbon atoms in a chain base structure with a nitrogen atom attached to one carbon of the 12 carbon atoms in the chain base structure, the nitrogen atom forming a part of the chain base structure and further attached to at least one of a separate carbon and an oxygen so that the nitrogen atom is not a terminal nitrogen atom and is not at any terminus of the active constituent, the active constituent lacking any amine group at any end or terminus of the active constituent, wherein the active constituent is in an amount between about 0.001 wt.% and about 30 wt.% based on total weight of composition in a suspension; a lipid selected from one or more from the group consisting of lecithin, phosphatidylcholine (PC), concentrated lecithin containing up to 25% PC, concentrated lecithin containing up to 40% PC, a mixture of glycerophospholipids, a phosphatide mixture comprising 25% to 95% PC, a lecithin containing acetone insoluble phosphatides, and combinations thereof, wherein the lipid is in an amount between about 0.01 wt.% and about 50 wt.% based on total weight of the liposomal composition in the suspension; a biopolymer comprising one or more from the group consisting of monosaccharide, polysaccharide, and mixtures thereof, wherein the biopolymer is in an amount between about 0.01 wt.% and about 40 wt.% based on total weight of the liposomal composition in suspension; and a suspension solution, wherein the suspension solution is in an amount between about 50 wt.% and about 99.9 wt.% based on total weight of the liposomal composition in the suspension.

2. The liposomal composition of any of claim 1, wherein the suspension solution is selected from the group consisting of sterile water, distilled water, pure water, a mild acidic buffer, an isotonic solution, normal saline solution, dextrose solution, Ringer's solution, lactated Ringer's solution, a hypotonic solution, hypotonic saline solution, hypotonic dextrose solution, a hypertonic solution, hypertonic saline solution, hypertonic dextrose solution and a phosphate buffered saline solution.

3. The liposomal composition of any of claim 1 or claim 2, wherein the biopolymer is selected from one or more from the group consisting of a chitosan, a cellulose, a hydroxypropyl methylcellulose, a carrageenan, an alginate, a guar gum, a polylysine, a poly(L)lysine,poly(L-glutamic acid, a poly(hyroxyethyl-l-asparagine, a xanthum gum, a gellan gum, a mixture of monosaccharides, starch, pectin, low methoxyl pectin, and pull u Ian.

4. The liposomal composition of any of claims 1 to 3, wherein the lecithin contains a mixture selected from two or more from the group consisting of phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, phosphatidic acid, phosphatidylserine, lysophospholipidsbulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, carbohydrates, and any combination thereof.

5. The particle-containing composition of any of claims 1 to 4, wherein phosphatide mixture contains phospholipids selected from the group consisting of glycerophospholipids, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, phosphatidic acid, phosphatidylserine, sphingomyelin, sphingolipids, lecithin, and any combination thereof.

6. The liposomal composition of any of claims 1 to 5, wherein the biopolymer is deacetylated chitosan, and the deacetylated chitosan is any one or more of a low molecular weight chitosan, a medium molecular weight chitosan, and a high molecular weight chitosan.

7. The liposomal composition of any of claims 1 to 6, wherein the liposomal composition further comprises one or more pharmaceutically acceptable excipients.

8. The liposomal composition of any of claims 1 to 7, wherein the liposomal composition is one or more of a pharmaceutical composition and a medicament.

9. The liposomal composition of any of claims 1 to 8, wherein the liposomal composition is part of a kit comprising the liposomal composition in a pharmaceutically acceptable formulation, and instructions for use of the pharmaceutically acceptable formulation.

10. The liposomal composition of any of claims 1 to 9, wherein the active constituent is at least one from the group selected from 12-(Boc-amino)dodecanoic acid and N,N-dimethyldodecylamine N-oxide.

11. The liposomal composition of any of claims 1 to 10, wherein the liposomal composition is in a formulation utilized as an antimicrobial against one or more Gram-negative bacterial pathogens selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL- producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL-producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem-resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem- resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains).

12. The liposomal composition of any of claims 1 to 11, wherein the liposomal composition is in a formulation utilized as an antimicrobial against one or more Gram-positive bacterial pathogens selectedfrom the group consisting of Enterococcus faecium (including vancomycin-resistant strains),Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains),Streptococcus pyogenes (including penicillin-non-susceptible strains), Streptococcus anginosus(including penicillin-non-susceptible strains).

13. The liposomal composition of any of claims 1 to 12, wherein the liposomal composition is in a formulation utilized as an antimicrobial against one or more fungal pathogens selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis,Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp.(e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma).

14. The liposomal composition of any of claims 1 to 13, wherein the liposomal composition is in a formulation utilized to disturb or inhibit formation of a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae,Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

15. The liposomal composition of any of claims 1 to 14, wherein the liposomal composition is in a formulation utilized as an antimicrobial against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

16. The liposomal composition of any of claims 1 to 15, wherein the liposomal composition is in the form of nanoparticles after performing a method that comprises vigorously stirring the active constituent, the lipid and the biopolymer in the suspension solution for up to 24 hours and collecting the nanoparticles after a filtration step, wherein the nanoparticles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, aggregates thereof, and combinations thereof.

17. An antimicrobial composition comprising: an active constituent, wherein the active constituent is selected from a group consisting of 12-(Boc-amino)dodecanoic acid (BOA) and any tautomeric forms of BOA, wherein BOA has a structure (1)a lipid, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide;wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against a pathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

18. The antimicrobial composition of claim 17, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-negative bacteria selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL-producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL- producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem- resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem-resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains), and combinations thereof.

19. The antimicrobial composition of any of claims 17 and 18, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-positive bacteria is selected from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes (including penicillin-non-susceptible strains), Streptococcus anginosus (including penicillin-non- susceptible strains), and combinations thereof.

20. The antimicrobial composition of any of claims 17 to 19, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the fungus is selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillusfumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma), and combinations thereof.

21. The antimicrobial composition of any of claims 17 to 19, wherein the antimicrobial composition is in a formulation utilized to disturb or inhibit formation of a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae, and combinations22. The antimicrobial composition of any of claims 17 to 21, wherein the antimicrobial composition is in a formulation and utilized against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

23. The antimicrobial composition of any of claims 17 to 22, wherein the biopolymer is selected from one or more from the group consisting of chitosan, cellulose, hydroxypropyl methylcellulose, carrageenan, alginate, guar gum, polylysine, poly(L)lysine, poly(L-glutamic acid), poly(hyroxyethyl-l- asparagine, xanthum gum, gellan gum, a mixture of monosaccharides including L-fucose, galactose, glucose and glucuronic acid, starch, pectin, low methoxyl pectin, and pullulan.

24. The antimicrobial composition of any of claims 17 to 23, wherein the lipid is from an animal or plant source and is selected from one or more from the group consisting of phosphatidylcholine (PC); PC mixed with other phosphatides, in which PC is up to 25% of the mixture; PC mixed with other phosphatides, in which PC is up to 40% of the mixture; lecithin; lecithin comprising acetone insoluble phospholipids; concentrated lecithin; a combination of one or more lecithin components selected from the group consisting of phosphatidylethanolamine, phosphatidylinositol, PC, phosphatidic acid, phosphatidylserine, lysophospholipids, bulky fatty acids, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, and carbohydrates; a combination selected from one or more from the group consisting of glycerophospholipids, lysophospholipids, bulky fatty acids, sterols, fatty acids having a chain length predominantly from about C-14 to C-20; a mixture of naturally occurring glycerophospholipids; PC combined with one or more from the group selected from bulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, carbohydrates; a lecithin concentrate in which PC is up to 25% of the concentrate; a lecithin concentrate in which PC is up to 40% of the concentrate.

25. An antimicrobial composition comprising: an active constituent, wherein the active constituent is selected from a group consisting of N,N- dimethyldodecylamine N-oxide (LO) and any tautomeric forms of LO, wherein LO has a structure (2)a lipid, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide; wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against a pathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

26. The antimicrobial composition of claim 25, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-negative bacteria selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL-producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL- producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem- resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem-resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (including ampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains), and combinations thereof.

27. The antimicrobial composition of any of claims 25 and 26, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-positive bacteria is selected from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes(including penicillin-non-susceptible strains), Streptococcus anginosus (including penicillin-non- susceptible strains), and combinations thereof.

28. The antimicrobial composition of any of claims 25 to 27, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the fungus is selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma), and combinations thereof.

29. The antimicrobial composition of any of claims 25 to 27, wherein the antimicrobial composition is in a formulation utilized to disturb or inhibit formation a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae, and combinations30. The antimicrobial composition of any of claims 25 to 29, wherein the antimicrobial composition is in a formulation and utilized against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

31. The antimicrobial composition of any of claims 25 to 30, wherein the biopolymer is selected from one or more from the group consisting of chitosan, cellulose, hydroxypropyl methylcellulose, carrageenan, alginate, guar gum, polylysine, poly(L)lysine, poly(L-glutamic acid), poly(hyroxyethyl-l- asparagine, xanthum gum, gellan gum, a mixture of monosaccharides including L-fucose, galactose, glucose and glucuronic acid, starch, pectin, low methoxyl pectin, and pullulan.

32. The antimicrobial composition of any of claims 25 to 31, wherein the lipid is from an animal or plant source and is selected from one or more from the group consisting of phosphatidylcholine (PC); PC mixed with other phosphatides, in which PC is up to 25% of the mixture; PC mixed with other phosphatides, in which PC is up to 40% of the mixture; lecithin; lecithin comprising acetone insoluble phospholipids; concentrated lecithin; a combination of one or more lecithin components selected from the group consisting of phosphatidylethanolamine, phosphatidylinositol, PC, phosphatidic acid, phosphatidylserine, lysophospholipids, bulky fatty acids, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, and carbohydrates; a combination selected from one or more from the group consisting of glycerophospholipids, lysophospholipids, bulky fatty acids, sterols, fatty acids having a chain length predominantly from about C-14 to C-20; a mixture of naturally occurring glycerophospholipids; PC combined with one or more from the group selected from bulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 toC-20, triglycerides, carbohydrates; a lecithin concentrate in which PC is up to 25% of the concentrate; a lecithin concentrate in which PC is up to 40% of the concentrate.

33. A medicament for use as an antimicrobial, the medicament comprising: an active constituent, wherein the active constituent is selected from one or more from a group consisting of: (a) 12-(Boc-amino)dodecanoic acid (BOA) and any tautomeric forms of BOA, wherein BOA has a structure (1)(1).and (b) N / N.dimethyldodecylamine N-oxide(LO) and any tautomeric forms of LO, wherein LO has a structure (2)a lipid, wherein the lipid comprises one or more phospholipids, and the lipid is selected for utilization in liposome formation; and a biopolymer, wherein the biopolymer is a polysaccharide; wherein the active constituent, lipid, and biopolymer are contained in particles, and wherein the particles are in a form selected from one or more from the group consisting of liposomes, vesicles, micelles, and aggregates thereof, and any combination thereof, wherein the particles are utilized in a formulation as an antimicrobial agent for antimicrobial activity against a pathogenic microorganism selected from one or more from a group consisting of Gram-positive bacteria, Gram-negative bacteria, fungus, and fungi.

34. The medicament of claim 33, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-negative bacteria selected from the group consisting of Escherichia coli (including carbapenem-resistant strains, ESBL-producing strains), Pseudomonas aeruginosa (including carbapenem-resistant strains), Klebsiella pneumonia (including carbapenem-resistant strains, ESBL- producing strains), Enterobacter cloacae (including carbapenem-resistant strains), Enterobacter aerogenes (including carbapenem-resistant strains), Serratia marcescens (including carbapenem- resistant strains, ESBL-producing strains), Proteus mirabilis (including carbapenem-resistant strains, ESBL-producing strains), Proteus vulgaris (including carbapenem-resistant strains, ESBL-producing strains), Morganella morganii (including carbapenem-resistant strains, ESBL-producing strains), Helicobacter pylori (including clarithromycin-resistant strains), Campylobacter jejuni (including fluoroquinolone-resistant strains), Salmonella enteritidis (including fluoroquinolone-resistant strains, Salmonella enterica (including fluoroquinolone-resistant strains), Neisseria gonorrhoeae (including cephalosporin-resistant strains, fluoroquinolone resistant strains), Haemophilus influenza (includingampicillin-resistant strains), and Shigella dysenteriae (including fluoroquinolone-resistant strains), and combinations thereof.

35. The medicament of any of claims 33 and 34, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the Gram-positive bacteria is selected from the group consisting of Enterococcus faecium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains, vancomycin intermediate and resistant strains), Streptococcus pneumoniae (including penicillin-non-susceptible strains), Streptococcus pyogenes (including penicillin-non- susceptible strains), Streptococcus anginosus (including penicillin-non-susceptible strains), and combinations thereof.

36. The medicament of any of claims 33 to 35, wherein the pathogenic microorganism is selected from one or more from the group consisting of Gram-positive bacteria, Gram-negative bacteria, and fungus, and wherein the fungus is selected from the group consisting of Candida species: Candida albicans Candida auris, Candida glabrata, Candida tropicalis, Candida parapsilosis; Aspergillus fumigatus; Cryptococcus neoformans; Fusarium spp.; Histoplasma spp. (e.g., capsulatum); and Eumycetoma causative agents (including fungi causing mucormycosis or mycetoma), and combinations thereof.

37. The medicament of any of claims 33 to 36, wherein the antimicrobial composition is in a formulation utilized to disturb or inhibit a bacterial biofilm produced by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae, and combinations thereof.

38. The medicament of any of claims 33 to 37, wherein the antimicrobial composition is in a formulation and utilized against a bacterial biofilm infection caused by one or more bacteria selected from the group consisting of S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus pneumoniae.

39. The medicament of any of claims 33 to 38, wherein the biopolymer is selected from one or more from the group consisting of chitosan, cellulose, hydroxypropyl methylcellulose, carrageenan, alginate, guar gum, polylysine, poly(L)lysine, poly(L-glutamic acid), poly(hyroxyethyl-l-asparagine, xanthum gum, gellan gum, a mixture of monosaccharides including L-fucose, galactose, glucose and glucuronic acid, starch, pectin, low methoxyl pectin, and pullulan.

40. The medicament of any of claims 33 to 39, wherein the lipid is from an animal or plant source and is selected from one or more from the group consisting of phosphatidylcholine (PC); PC mixed with other phosphatides, in which PC is up to 25% of the mixture; PC mixed with other phosphatides, in which PC is up to 40% of the mixture; lecithin; lecithin comprising acetone insoluble phospholipids;concentrated lecithin; a combination of one or more lecithin components selected from the group consisting of phosphatidylethanolamine, phosphatidylinositol, PC, phosphatidic acid, phosphatidylserine, lysophospholipids, bulky fatty acids, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, and carbohydrates; a combination selected from one or more from the group consisting of glycerophospholipids, lysophospholipids, bulky fatty acids, sterols, fatty acids having a chain length predominantly from about C-14 to C-20; a mixture of naturally occurring glycerophospholipids; PC combined with one or more from the group selected from bulky fatty acids, sterols, choline, choline esters, fatty acids having a chain length predominantly from about C-14 to C-20, triglycerides, carbohydrates; a lecithin concentrate in which PC is up to 25% of the concentrate; a lecithin concentrate in which PC is up to 40% of the concentrate.

41. The medicament of any of claims 33 to 40, wherein the medicament further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of suspending solution, sugar, starch, cellulose, fat, wax, paraffin, oil, glycol, fatty acid ester, buffering agent, filler, absorbent, binder, humectant, disintegrating agent, lubricant, releasing agent, preservative, and coating agent, sweetener, colorant, flavorant, and antioxidant.

42. The liposomal composition of any of claims 1-16, the antimicrobial compositions of any of claims 17 to 32, and the medicament of any of claims 33 to 41, wherein any of the liposomal composition, the antimicrobial compositions, and the medicament are utilized in a formulation for one or more from the groups selected from: (a) delivering as an antimicrobial to one or more target pathogenic microbial cells;(b) providing as an antimicrobial to an outer membrane of one or more target pathogenic microbial cells;(c) delivering to one or more target pathogenic microbial cells by administering to a subject having or suspected of having the target pathogenic microbial cells; (d) providing as an antimicrobial for therapeutic use against one or more target pathogenic microbial cells; (e) providing as an antimicrobial for inhibiting growth of one or more target pathogenic microbial cells; and (f) providing in a kit having instructions for use.

43. The liposomal composition of any of claims 1-16, the antimicrobial compositions of any of claims 17 to 32, and the medicament of any of claims 33 to 41, wherein the formulation is sufficient for administering as at least one or more doses to a subject in need, the administering being selected from any one or more from the group consisting of orally, rectally, parenterally, intracisternally, intramuscularly, intravaginally, intraperitoneally, topically, bucally, nasally, or by enema.