Antimicrobial constructs
Inventors
Neff, Jennifer A. • McGuire, Joseph • Joshi, Pranav R.
Assignees
Oregon State Board of Higher Education • Oregon State University • ALLVIVO VASCULAR Inc
Publication Number
US-8178617-B2
Publication Date
2012-05-15
Expiration Date
2028-07-11
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Abstract
The invention is based on the recognition that known antimicrobial compounds, such as nisin or other lantibiotics, can be made to form a long lasting antimicrobial surface coating by linking the peptide with a block polymer, such as PLURONIC® F108 or an end group activated polymer (EGAP) in a manner to form a flexible tether and/or entrap the peptide. The entrapped peptide provides antimicrobial action by early release from entrapment while the tethered peptide provides longer lasting antimicrobial protection. Antimicrobial gels and foams may be prepared using the antimicrobial peptide containing block copolymers.
Core Innovation
The invention provides antimicrobial constructs by combining known antimicrobial peptides, such as nisin or other lantibiotics, with block copolymers like PLURONIC® F108 or end group activated polymers (EGAPs). By linking the peptide with the copolymer to form a flexible tether and/or entrapment, the resulting constructs generate surfaces, gels, foams, and other products with both protein-resistant and antimicrobial properties.
This approach addresses persistent problems in medical and material science, such as infection, biofilm formation, device occlusion, and bacterial resistance, by providing an antimicrobial surface that releases active agent early through entrapment and ensures long-term activity via tethered peptides. The coating prevents bacteria adhesion, reduces protein adsorption, and retains the antimicrobial efficacy of the peptide while enhancing its stability and retention on surfaces.
The constructs can be applied to various substrates, including medical devices and food packaging, as coatings, or incorporated into creams, gels, foams, and powders for topical or other uses. The method of application involves steps such as dip-coating or sequential exposure to copolymer and peptide solutions, ensuring that the antimicrobial activity is provided at the interface of the material with biological environments while maintaining biocompatibility.
Claims Coverage
The patent claims cover multiple inventive features related to antimicrobial block copolymer constructs and their methods of formation and applications.
Antimicrobial block copolymer construct with tethered and entrapped antimicrobial component
An antimicrobial block copolymer construct comprising an antimicrobial component, wherein a quantity of the antimicrobial component is attached to the block copolymer to form a flexible tether and another quantity is physically entrapped in the polymer chains. The block copolymer provides early antimicrobial activity by releasing the entrapped antimicrobial component and prolonged activity through the tethered component.
Block copolymer with functional group for ionic interactions
The block copolymer construct includes a functional group enabling ionic interactions.
Antimicrobial block copolymer with defined hydrophilic and hydrophobic regions
An antimicrobial block copolymer construct in which the antimicrobial component is a peptide and the block copolymer contains hydrophilic regions and hydrophobic regions.
Block copolymers comprising specific polymer units
The block copolymer may comprise polymer units selected from: polyethylene oxide (PEO) and polypropylene oxide (PPO), PEO and polybutylene oxide, PEO and polybutadiene, PEO and poly(N-acetylethyleneimine), PEO and polyurethane, PEO and polymethylmethacrylate (PMMA), PEO and poly (ε-caprolactone), PEO and poly lactide, PEO and poly (lactide-co-glycolide), PEO and polydimethyl siloxane, poly phosphoester and various other named polymers.
Application to substrates and various formulations
The block copolymer constructs can be coated on substrates or included in solutions, gels, foams, emulsions, or powders.
Methods of forming antimicrobial coatings
Methods for forming antimicrobial coatings including: (a) forming an antimicrobial construct with the copolymer and antimicrobial component (with both tethered and entrapped portions), then exposing the substrate to this construct; (b) forming a second block copolymer construct containing a metal chelating agent and adhering it to the substrate; (c) exposing the substrate to a block copolymer solution to coat it, followed by exposing it to an antimicrobial peptide solution for covalent attachment and entrapment.
Block copolymer constructs with phenyl boronic acid
The block copolymer may further comprise phenyl boronic acid.
Antimicrobial coatings as crosslinked networks
An antimicrobial coating comprising a substrate with a coating of block copolymer in the form of a crosslinked network, containing hydrophilic and hydrophobic regions, with the antimicrobial component tethered and entrapped as previously described.
The patent claims inventive features including antimicrobial constructs that combine tethered and entrapped antimicrobial components with block copolymers possessing hydrophilic and hydrophobic regions, specific functional groups, and multiple formulation and application methods.
Stated Advantages
Incorporates a natural antibacterial component that is not likely to stimulate bacterial resistance.
Combines surface properties that help prevent fibrin formation and occlusion.
Is biocompatible and can be directly interfaced with tissue.
Can be readily applied to a variety of materials and irregularly shaped objects.
PEO chains inhibit spontaneous elution and confer stability toward conformational rearrangement, leading to improved retention of activity.
Does not risk decreasing the potency of limited forms of clinical antibiotics.
Allows for broader use, increased safety, and reduced medical cost.
Documented Applications
Coating medical devices, such as catheters, vascular access devices, drug delivery pumps, drug reservoirs, encapsulation devices, transcutaneous devices, neural stimulation or intervention devices, intubation tubes, sutures, shunts, drainage tubes, feeding tubes, orthopedic devices, dental devices, extracorporeal circulation devices, tubing, fittings, luer locks, optical devices, and other medical devices that contact the body or body fluids.
Coating tissue products such as heart valves.
Coating storage containers for food packaging, blood bags, proteins, or pharmaceuticals.
Solutions for cleaning medical equipment, sterile environments, or food preparation equipment.
Coatings for personal or industrial products including mouth guards, orthodontic devices, dental mouth pieces, face or breathing masks, pacifiers, contact lenses, adult products, food preparation surfaces, reusable water containers, sports hydration systems, water bottles, computer keyboards, telephones, car steering wheels, health club equipment, whirlpool spas, humidifiers, decorative fountains, and hot water tanks.
Coatings for cooling towers, whirlpool spas, steam baths, filtration devices, and water lines used in medical or sterile manufacturing environments.
Food industry use, including coating food products and packaging to provide antimicrobial activity.
Wound healing gels, with possible inclusion of growth factors or anti-inflammatory agents, for use on diabetic ulcers, burns, and surgery sites.
Foam cleaning solutions for surfaces.
Prevention of surgical adhesions by coating related materials.
Addition to oral care products like toothpaste or mouth wash to provide lasting protection from tooth decay.
Coating tissue scaffolds with antimicrobial block copolymer constructs for biomedical applications.
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