Showing papers by "Yi Yan Yang published in 2017"

Short Synthetic β-Sheet Antimicrobial Peptides for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Burn Wound Infections

Abstract: Pseudomonas aeruginosa is often implicated in burn wound infections; its inherent drug resistance often renders these infections extremely challenging to treat. This is further compounded by the problem of emerging drug resistance and the dearth of novel antimicrobial drug discovery in recent years. In the perennial search for effective antimicrobial compounds, the authors identify short synthetic β-sheet folding peptides, IRIKIRIK (IK8L), IRIkIrIK (IK8-2D), and irikirik (IK8D) as prime candidates owing to their high potency against Gram-negative bacteria. In this study, the peptides are first assayed against 20 clinically isolated multidrug-resistant P. aeruginosa strains in comparison with the conventional antibiotics imipenem and ceftazidime, and IK8L is demonstrated to be the most effective. IK8L also exhibits superior antibacterial killing kinetics compared to imipenem and ceftazidime. From transmission electron microscopy, confocal microscopy, and protein release analyses, IK8L shows membrane-lytic antimicrobial mechanism. Repeated use of IK8L does not induce drug resistance, while the bacteria develop resistance against the antibiotics after several times of treatment at sublethal doses. Analysis of mouse blood serum chemistry reveals that peptide does not induce systemic toxicity. The potential utility of IK8L in the in vivo treatment of P. aeruginosa-infected burn wounds is further demonstrated in a mouse model.

Non-Isocyanate Polyurethane Soft Nanoparticles Obtained by Surfactant-Assisted Interfacial Polymerization.

Abstract: Polyurethanes (PUs) are considered ideal candidates for drug delivery applications due to their easy synthesis, excellent mechanical properties, and biodegradability. Unfortunately, methods for preparing well-defined PU nanoparticles required miniemulsion polymerization techniques with a nontrivial control of the polymerization conditions due to the inherent incompatibility of isocyanate-containing monomers and water. In this work, we report the preparation of soft PU nanoparticles in a one-pot process using interfacial polymerization that employs a non-isocyanate polymerization route that minimizes side reactions with water. Activated pentafluorophenyl dicarbonates were polymerized with diamines and/or triamines by interfacial polymerization in the presence of an anionic emulsifier, which afforded non-isocyanate polyurethane (NIPU) nanoparticles with sizes in the range of 200–300 nm. Notably, 5 wt % of emulsifier was required in combination with a trifunctional amine to achieve stable PU dispersions and ...

Self-Assembled, Biodegradable Magnetic Resonance Imaging Agents: Organic Radical-Functionalized Diblock Copolymers

Abstract: We report the design, synthesis, and evaluation of biodegradable amphiphilic poly(ethylene glycol)-b-polycarbonate-based diblock copolymers containing pendant persistent organic radicals (e.g., PROXYL). These paramagnetic radical-functionalized polymers self-assemble into micellar nanoparticles in aqueous media, which preferentially accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect. Through T1 relaxation NMR studies, as well as magnetic resonance imaging (MRI) studies on mice, we show that these nanomaterials are effective as metal-free, biodegradable MRI contrast agents. We also demonstrate anticancer drugs can be readily loaded into the nanoparticles, conferring therapeutic delivery properties in addition to their imaging properties making these materials potential theranostic agents in the treatment of cancer.

Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy

Abstract: In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability. In addition, the macromolecular antimicrobial is less likely to induce resistance as it acts via a membrane-lytic mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0 ± 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream infection mouse model, the polymer removes bacteria from the blood more rapidly than the antibiotic Augmentin. At the effective dose, the polymer treatment does not damage liver and kidney tissues or functions. In addition, blood electrolyte balance remains unchanged after the treatment. The low cost of starting materials, ease of synthesis, nontoxicity, broad spectrum activity with fast killing kinetics, and in vivo antimicrobial activity make these macromolecular antimicrobials ideal candidates for prevention of sepsis and treatment of infections.

Preparation of Biodegradable Cationic Polycarbonates and Hydrogels through the Direct Polymerization of Quaternized Cyclic Carbonates

Abstract: Polymers exhibiting both antimicrobial and biodegradable properties are of great interest for next generation materials in healthcare. Among those, cationic polycarbonates are one of the most promising classes of materials because of their biodegradability, low toxicity, and biocompatibility. They are typically prepared by a chemical postmodification after the polymer has been synthesized. The main problem with the latter is the challenges of ensuring and verifying complete quaternization within the polymer structure. Herein, we report the first example of synthesizing and polymerizing charged aliphatic cyclic carbonates with three different alkane pendant groups (N-methyl, N-butyl, and N-hexyl) by ring-opening polymerization (ROP). These charged eight-membered cyclic carbonates displayed extraordinary reactivity and were even polymerizable in polar solvents (e.g., DMSO) and in catalyst free conditions that are generally unobtainable for other ring opening polymerization processes. A computational study w...

Short Synthetic α‐Helical‐Forming Peptide Amphiphiles for Fungal Keratitis Treatment In Vivo

Abstract: The emergence of fungal keratitis is on the rise globally. However, current antifungal therapeutics are ineffective in severe keratomycosis. Previously reported α-helical peptides comprising 8-14 amino acids demonstrate broad-spectrum antimicrobial activity both in vitro and in vivo. Here, α-helical peptides of the optimized sequences are investigated for antifungal biofilm in vitro and in vivo using a fungal biofilm-caused mouse keratitis model. The peptides with the optimal composition demonstrate higher α-helical propensity and improve antifungal activity in dispersing Candida albicans biofilm in vitro. Moreover, the optimized α-helical peptides are not only effective in treating C. albicans biofilm-induced keratitis in mice, they are also nontoxic to the mice eyes. These peptides have the potential to be developed as antifungal agents for the treatment of C. albicans biofilm-caused keratitis.

Self-Assembly and Dynamics Driven by Oligocarbonate–Fluorene End-Functionalized Poly(ethylene glycol) ABA Triblock Copolymers

Abstract: The closed assembly transition from polymers to micelles and open assembly to clusters are induced by supramolecular π–π stacking in model oligocarbonate–fluorene (F-TMC) end-group telechelic polymers. The critical micelle concentration (CMC) depends on the F-TMC degree of polymerization that further controls the weak micelle association and strong clustering of micelles regimes. Clustering follows a multistep equilibria model with average size scaling with concentration reduced by the CMC as R ∼ (c/CMC)1/4. The F-TMC packing that drives the supramolecular self-assembly from polymers to micelles stabilizes these larger clusters. The clusters are characterized by internal relaxations by dynamic light scattering. This signifies that while F-TMC groups drive the clustering, the micelles interconnected via F-TMC bridging interactions remain coupled to the extent that the clusters relax via Rouse–Zimm dynamics, reminiscent of microgels.

Convergent Approach to Boronic Acid Functionalized Polycarbonates: Accessing New Dynamic Material Platforms

Abstract: Polycarbonates are routinely utilized for diverse medicinal applications and are highly efficacious scaffolds for drug delivery and antimicrobial treatments. In order to provide for robust, dynamic platforms for biomedical applications, we have developed new routes for the incorporation of boronic acids into the polycarbonate backbone. These routes take advantage of straightforward postsynthesis modification of established polycarbonate backbones, enabling the preparation of a diverse array of boronic acid functionalized polycarbonates from readily accessible polycarbonates. In particular, this approach circumvents the need for de novo monomer synthesis, functional group incompatibilities, and deprotection steps that often limit other methods. This strategy has been demonstrated using a broad array of unprotected boronic acids to produce both neutral and cationic boronic acid functionalized polycarbonates.

Polythioaminals and Uses Thereof

Abstract: wherein each R1 is independently an organic or hetero-organic group, each R2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Highly hydrophobic antifouling coatings for implantable medical devices

Abstract: Antibacterial coatings and methods of making the antibacterial coatings are described herein. In particular, a method for forming an organocatalyzed polythioether coating is provided in which a first solution including a bis-silylated dithiol and a fluoroarene is prepared. A second solution including an organocatalyst is prepared. The first solution and the second solution are mixed to form a mixed solution. The mixed solution is applied to a substrate, and the substrate is cured.

Prevention of biofilm formation

Abstract: Antibacterial coatings and methods of making the antibacterial coatings are described herein. A first branched polyethylenimine (BPEI) layer is formed and a first glyoxal layer is formed on a surface of the BPEI layer. The first BPEI layer and the first glyoxal layer are cured to form a crosslinked BPEI coating. The first BPEI layer can be modified with superhydrophobic moieties, superhydrophilic moieties, or negatively charged moieties to increase the antifouling characteristics of the coating. The first BPEI layer can be modified with contact-killing bactericidal moieties to increase the bactericidal characteristics of the coating.

Fluorinated networks for anti-fouling surfaces

Abstract: According to one or more embodiments, a method of making an antifouling coating includes forming a polythioaminal polymer by reacting a fluorinated primary amine with an aldehyde to form an intermediate imine, and then reacting the intermediate imine with a dithiol. The method further includes depositing the polythioaminal on a substrate, and increasing a temperature of the polythioaminal deposited on the substrate to crosslink the polythioaminal and increase a contact angle of the substrate with crosslinked polythioaminal.

Chemical compositions with antimicrobial functionality

Abstract: Techniques regarding killing of a pathogen with one or more ionene compositions having antimicrobial functionality are provided. For example, one or more embodiments can comprise a method, which can comprise contacting a Mycobacterium tuberculosis microbe with a chemical compound. The chemical compound can comprise an ionene unit. Also, the ionene unit can comprise a cation distributed along a molecular backbone. The ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of the Mycobacterium tuberculosis microbe in response to the contacting.

Star polymers with enhanced antimicrobial activity in response to light

Abstract: Techniques regarding star polymers with enhanced antimicrobial functionality are provided. For example, a polymer is provided that can comprise a core that can have a singlet oxygen generator and that can generate a singlet oxygen species upon irradiation with light. The polymer can also comprise a plurality of polycarbonate arms covalently bonded to the core. The plurality of polycarbonate arms can be degradable and can comprise a cation. Further, the plurality of polycarbonate arms can have antimicrobial functionality.

Antimicrobial polymers capable of supramolecular assembly

Abstract: Techniques regarding chemical compounds with antimicrobial functionality are provided. For example, one or more embodiments describe herein can comprise a monomer that can comprise a molecular backbone. The molecular backbone can comprise a bis(urea)guanidinium structure covalently bonded to a functional group, which can comprise a radical. Also, the monomer can have supramolecular assembly functionality.

Hydrophilic polymers with antimicrobial functionalities

Abstract: Techniques regarding ionene and/or polyionene compositions with antimicrobial functionality and enhanced hydrophilicity are provided. For example, one or more embodiments can regard a chemical compound that can comprise an ionene unit, which can comprise a cation distributed along a degradable backbone. The degradable backbone can comprise a terephthalamide structure. The ionene unit can have antimicrobial functionality. Further, the chemical compound can comprise a hydrophilic functional group covalently bonded to the ionene unit. Also, the chemical compound can have carbohydrate mimetic functionality.

Preparation of robust polythioaminal carriers

Abstract: The present disclosure relates to polythioaminals with applications as carriers or delivery vehicles for therapeutic agents or other small molecule cargo. Polythioaminal block copolymer coupled to a therapeutic agent is a polymer-therapeutic conjugate that exhibits higher stability and longer life time in aqueous environments. The polythioaminal block copolymer coupled to a therapeutic agent can be synthesized by reacting hexahydrotriazines with a hydrophobic block precursor, a hydrophilic block precursor, a particle stabilizing segment precursor, and a cargo, such as a therapeutic agent, in a one pot synthesis. The ease of synthesizing the resulting polythioaminal block copolymer coupled to the therapeutic agent while offering the extended stability and polymer life time in aqueous environments make the polythioaminal block copolymer particularly attractive for therapeutic carriers.

Antimicrobial ionene compositions with a variety of functional groups

Abstract: Techniques regarding amine monomers that can form ionene compositions with antimicrobial functionality are provided. For example, one or more embodiments described herein can comprise a monomer, which can comprise a molecular backbone. The molecular backbone can comprise a norspermidine structure. The norspermidine structure can comprise a tertiary amino group. Also, the tertiary amino group can comprise a functional group, and an amino group of the norspermidine structure can be capable of being ionized.

Antimicrobial polymers with enhanced functionalities

Abstract: Techniques regarding ionene and/or polyionene compositions with antimicrobial functionalities are provided. For example, one or more embodiments can comprise a chemical compound, which can comprise an ionene unit. The ionene unit can comprise a cation distributed along a degradable backbone. The degradable backbone can comprise a norspermidine structure having a carbonyl group. Also, the ionene unit can have antimicrobial functionality.

Monomer compositions with antimicrobial functionality

Abstract: Techniques regarding ionene compositions with antimicrobial functionality are provided For example, one or more embodiments can comprise a monomer, which can comprise a single ionene unit The single ionene unit can comprise a cation distributed along a molecular backbone Also, a hydrophobic functional group can be covalently bonded to the molecular backbone, and the single ionene unit can have antimicrobial functionality

Polymers with antimicrobial functionalities

Abstract: Techniques regarding polymers with antimicrobial functionality are provided For example, one or more embodiments described herein can regard a polymer, which can comprise a repeating ionene unit The repeating ionene unit can comprise a cation distributed along a degradable backbone The degradable backbone can comprise a terephthalamide structure Further, the repeating ionene unit can have antimicrobial functionality

Block copolymers and self-assembling nanoparticles formed therefrom

Abstract: The subject matter of this invention relates to block copolymers (BCPs) and, more particularly, to block copolymers capable of self-assembly into nanoparticles for the delivery of hydrophobic cargos. The BCPs include a hydrophobic block that contains a thioether functional group that is susceptible to oxidation, transforming the solubility of the block from hydrophobic to hydrophilic, thereby releasing the hydrophobic cargo of the nanoparticle.