Anti-bacterial applications of poly-N-acetylglucosamine nanofibers
Inventors
Vournakis, John N. • Finkielsztein, Sergio
Assignees
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Publication Number
US-9642871-B2
Publication Date
2017-05-09
Expiration Date
Abstract
Described herein are compositions comprising shortened fibers of poly-N-acetylglucosamine and/or a derivative thereof (“sNAG nanofibers”) and anti-bacterial applications of such compositions. The sNAG nanofibers may be formulated into compositions for the prevention and/or treatment of bacterial infections and diseases associated with such infections. Regimens employing such compositions are also described.
Core Innovation
The invention relates to treating a disease or condition associated with a bacterial imbalance in a subject by topically administering a composition comprising shortened fibers of poly-β-1→4-N-acetylglucosamine (sNAG nanofibers). The sNAG nanofibers are less than 10 μm in length and comprise 70% or more than 70% of the N-acetylglucosamine monosaccharides. The sNAG nanofibers do not have an effect, or substantially have no effect, on bacterial growth or survival of Staphylococcus aureus bacterial cultures in vitro.
The invention further describes a non-direct antibacterial mechanism in which sNAG nanofibers stimulate innate immunity rather than substantially inhibit bacterial growth in vitro. This is associated with upregulating defensins, notably β-defensin 3, and Toll-like receptor pathway components via Akt1/Ets1 signaling, which leads to reduced bacterial burden and improved wound outcomes in vivo.
The disclosed compositions and topical formats include sNAG nanofibers as shortened poly-N-acetylglucosamine nanofibers for topical prevention or treatment of bacterial infections, including cutaneous wounds and microbiota-related diseases. The document also describes shortened fiber length distribution, irradiation-derived shortened fibers, and biocompatibility/non-reactivity concepts, supported by described in vitro and in vivo experimental results.
Claims Coverage
The independent claim covers a topical treatment method for a disease or condition associated with bacterial imbalance, using sNAG nanofibers with defined length and N-acetylglucosamine monosaccharide content, while excluding substantial in vitro effects on Staphylococcus aureus growth/survival. The main inventive features present in the independent claim are refined by dependent claims via additional constraints on fiber length and monosaccharide enrichment and by conditions on administration context such as omission of anti-bacterial agents.
Topical administration of shortened poly-β-1→4-N-acetylglucosamine fibers for bacterial imbalance
A method for treating a disease or a condition associated with a bacterial imbalance in a subject in need thereof, comprising topically administering a composition comprising shortened fibers of poly-β-1→4-N-acetylglucosamine ("sNAG nanofibers").
Defined fiber length and monosaccharide composition
The sNAG nanofibers are less than 10 μm in length, wherein the sNAG nanofibers comprise 70% or more than 70% of the N-acetylglucosamine monosaccharides.
No substantial in vitro effect on Staphylococcus aureus growth/survival
The sNAG nanofibers do not have an effect, or substantially have no effect, on bacterial growth or survival of Staphylococcus aureus bacterial cultures in vitro.
Across the independent claim, the invention is centered on topical treatment for bacterial imbalance using sNAG nanofibers that are shortened (<10 μm) and enriched in N-acetylglucosamine monosaccharides (≥70%), while avoiding substantial direct inhibition of Staphylococcus aureus growth or survival in vitro. Dependent claim refinements include narrower length and enrichment ranges and specify administration constraints such as excluding co-administration with an anti-bacterial agent.
Stated Advantages
Promotes cutaneous wound healing via Akt1→Ets1 signaling.
Upregulates defensins, notably β-defensin 3, in endothelial cells and keratinocytes.
Increases wound closure kinetics in a wild-type setting.
Reduces bacterial load in Staphylococcus aureus-infected wounds.
Blocks or abolishes the antibacterial effect when β-defensin 3 is neutralized, linking defensin activity to antibacterial outcome.
Provides defensin/TLR gene upregulation and an example of antibacterial activity against Pseudomonas aeruginosa.
Improved wound outcomes in vivo.
Reduced bacterial burden associated with innate immune stimulation.
Non-direct antibacterial activity characterized by no substantial effect on Staphylococcus aureus growth or survival in vitro.
Documented Applications
Topical administration for wound treatment, including cutaneous wounds and surgical sites.
Administration to genital/urinal/anal tissues.
Administration to the oral/respiratory tract as a spray or inhaler.
Use of rectal/vaginal/urethral suppositories.
Coating of a device for localized administration.
Use in sustained-release formulations and topical/localized dosing regimens.
Topical prevention or treatment of bacterial infections including cutaneous wounds.
Treatment of microbiota-related diseases associated with bacterial imbalance.
Diseases or conditions associated with bacterial imbalance in a subject, including contexts described in the document for pathogens such as Staphylococcus aureus/MRSA, Pseudomonas, and Clostridium difficile.
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