Antibacterial Silver Nanoparticle Containing Polydopamine Hydrogels That Enhance Re-Epithelization.

A polydopamine polyelectrolyte hydrogel was developed by ionic crosslinking dextran sulfate with a copolymer of polyethyleneimine and polydopamine. Gelation was promoted by the slow hydrolysis of glucono-δ-lactone. Within this hydrogel, silver nanoparticles were generated in situ, ranging from 25 nm to 200 nm in size. The antibacterial activity of the hydrogel was proportional to the quantity of silver nanoparticles produced, increasing as the nanoparticle count rose. The hydrogels demonstrated broad-spectrum antibacterial efficacy at concentrations up to 108 cells/mL for P. aeruginosa, K. pneumoniae, E. coli and S. aureus, the four most prevalent bacterial pathogens in chronic septic wounds. In ex vivo studies on human skin, biocompatibility was enhanced by the presence of polydopamine. Dextran sulfate is a known irritant, but formulations with polydopamine showed improved cell viability and reduced levels of the inflammatory biomarkers IL-8 and IL-1α. Silver nanoparticles can inhibit cell migration, but an ex vivo human skin study showed significant re-epithelialization in wounds treated with hydrogels containing silver nanoparticles.

Polydopamine Antioxidant Hydrogels for Wound Healing Applications.

Antioxidants are known to improve the wound healing process and are researched as a therapeutic strategy to treat chronic wounds. Dopamine is a known neurotransmitter with antioxidant properties that can be polymerized to form polydopamine (PDA). Herein, polydopamine is demonstrated as an antioxidant biomaterial. In prior work, we developed methodology to prepare hydrogels by crosslinking polysaccharides with polyamines via epichlorohydrin and NaOH. Using this previously developed methodology, dextran hydrogels crosslinked with polydopamine were prepared. Darkening of the gels indicated the increasing incorporation of polydopamine within the hydrogels. In addition to basic pH, polydopamine can be formed by reaction with polyethylene imine (PEI), which results in PEI-PDA copolymer. Dextran was similarly crosslinked with the PEI-PDA copolymer and resulted in sturdier, darker gels, which had more polydopamine incorporated. Hydrogel morphology and strength were dependent on the feed ratios of dopamine. Antioxidant activity of polydopamine containing hydrogel was confirmed and shown to be dependent on the amount of dopamine used in hydrogel synthesis. Hydrogels with 0.5 dopamine to dextran feed ratio scavenged 78.8% of radicals in a 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant assay while gels with no dopamine scavenged only 1.4% of radicals. An ex vivo wound healing assay showed considerable cell migration with the PEI-PDA containing hydrogel.

A Self-degradable Curcumin Polymer with Anti-cancer Activity.

Curcumin is a widely researched and utilized natural product used for a variety of ailments including as a gastrointestinal aide and an anticancer agent. Curcumin however suffers from poor bioavailability. A strategy to circumvent poor bioavailability is to administer with an adjuvant or by synthetic modification. Herein we demonstrate the incorporation of curcumin into a self-degradable polymer by condensation with N,N'-di-Boc-L-cystine. The polymer is made self-degradable upon deprotection of the cystine amines. Degradation is confirmed by thermogravimetric analysis and differential scanning calorimetry. Curcumin retains its anti-cancer activity within the polymer showing activity against HT29 human colon cancer cells and DU-145 prostate cancer cells. The self-degrading polymer showed enhanced activity against HT29 cells compared to that of curcumin.

Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic properties.

Amine functionalized polysaccharide hydrogels such as those based on chitosan are widely examined as biomaterials. Here we set out to develop a facile procedure for developing such hydrogels by crosslinking dextran with amino acid diamines. The dextran-amino acid gels were formed by the addition of the amino acid diamines to a dextran and epichlorohydrin solution once it became homogeneous. This was demonstrated with three amino acid diamines, lysine, lysine methyl ester, and cystine dimethyl ester. Hydrogel networks with albumin entrapped were also demonstrated. These hydrogels were characterized by FTIR, SEM, rotational rheometry, swelling studies and cell biocompatibility analysis. These hydrogels showed the unexpected pH-responsive behavior of greater swelling at more basic pH, similar to that of an anionic hydrogel. This is uncharacteristic for amine functionalized gels as they typically exhibit cationic hydrogel behavior. All hydrogels showed similar biocompatibility to that of dextran crosslinked without amino acids.

The crosslinking of polysaccharides with polyamines and dextran-polyallylamine antibacterial hydrogels.

A facile modular approach to rapidly prepare pH-responsive hydrogels by crosslinking polysaccharides with polyamines is demonstrated. Hydrogels are prepared by first reacting the less reactive polysaccharides with the cross-linker epichlorohydrin and completed by the addition of polyamines. The crosslinking of polysaccharides with polyamines provides a facile method for incorporating functionality into polysaccharide based hydrogels. This process is demonstrated with the polysaccharides dextran, pullulan and carboxymethyl cellulose and with the polyamines polyallylamine and polyethylene imine. The hydrogels were characterized by FTIR and swelling studies, which showed pH-dependent swelling due to the presence of the polyamine. The hydrogels can also be tailored by varying the mass ratio between the polysaccharide and polyamine. Absorption studies of organic analytes showed the polyamine content affecting the uptake of a charged substrate (methylene blue) and no effect on a neutral substrate (6-methyl coumarin). This synthetic method was also used to prepare hydrogels with antibacterial activity against E. coli and S. aureus by utilizing an amphiphilic polyallylamine.

Nitroalcohol Induced Hydrogel Formation in Amine-Functionalized Polymers.

Certain ß-nitroalcohols degrade under basic conditions or upon heating to form formaldehyde. This reaction provides an elegant approach to generate formaldehyde within a system at a desired time using the stimulus of pH or temperature. Using ß-nitroalcohols as a delivery agent for formaldehyde, polymer crosslinking can be induced via stimulus. Such an approach is akin to those used to prepare "self-healing" polymers, which have received much attention recently. Herein, we describe the use of certain ß-nitroalcohols as a masked formaldehyde delivery system and demonstrate its use as a crosslinking agent of amine functionalized polymers to form hydrogels. We examine the temperature and pH dependence of 2-nitro-1,3-propanediol and 2-(hydroxymethyl)-2-nitro-1,2-propanediol on the rate and extent of gelation and characterize the resulting gel by swelling and FTIR experiments.

A covalently linked phenanthridine-ruthenium(II) complex as a RNA probe.

A phenanthridine derivative covalently linked to a ruthenium complex yields an imaging probe whose fluorescence intensity and lifetime change substantially in the presence of RNA.

Screening of 5-HT1A receptor antagonists using molecularly imprinted polymers.

Molecular imprinting produces network polymers with recognition sites for imprint molecules. The high binding affinity and selectivity in conjunction with the polymers' physical robustness positions molecular imprinted polymers (MIPs) as candidates for use as preliminary screens in drug discovery. As such, MIPs can serve as crude mimics of native receptors. In an effort to evaluate the relationship between MIPs and native receptors, imprinted polymers for WAY-100635, an antagonist of the serotonin (5-HT) receptor subtype 5-HT1A were prepared. The resulting MIP P(WAY) was evaluated as an affinity matrix in the screening of serotonin receptor antagonists with known affinities for the native receptor. Rough correlations in affinity between the synthetic P(WAY) and native receptor 5-HT1A were found. These findings provide some support for the analogy between MIPs and native receptors and their possible use as surrogates.

Chemically modified dansyl probes: a fluorescent diagnostic for ion and proton detection in solution and in polymers.

[reaction: see text] The fluorescence emission intensity of the dansyl group is significantly diminished upon appending an ethyldimethylamino group to the N1 nitrogen substituent. Addition of acids and metal ions (i.e., Zn(2+)) to solutions of trimethylethylenediamine naphthalene sulfonamide (trinsyl) 2 produces a >25-fold increase in fluorescence intensity. Trinsyl probe 2 has been used as a diagnostic for the diffusion of protons and metal ions in a network polymer as well as an optical reporter for the glass transition temperature.