"Smart" polymer enhances the efficacy of topical antimicrobial agents.

The delivery of antimicrobial agents to surface wounds has been shown to be of central importance to the wound healing process. In this work, we prepared film forming wound care formulations containing 3 polymers (FTP) that provide broad-spectrum antimicrobial protection for prolonged periods. FTP formulations comprises of a smart gel matrix comprising of pH-degradable and temperature responsive polyacetals (smart polymer) which allow for the FTP films to be hydrophobic at room temperature, preventing accidental rubbing off, and hydrophilic at lower temperatures, allowing for easy removal. Two FTP smart-antimicrobial films were evaluated in this work: FTP-AgSD (Silver sulfadiazine actives), and FTP-NP (Neosporin actives). The in vitro and ex vivo antimicrobial efficacy studies show that FTP-AgSD films are significantly more effective for longer durations against Staphylococcus aureus (3 days), Candida albicans (9 days) and Pseudomonas aeruginosa (4 days) when compared to the cream formulations containing antimicrobials. FTP-NP films showed significantly improved antimicrobial activity for a minimum of 3 days for all pathogens tested. Moreover, when tested ex vivo in porcine skin, FTP-AgSD and FTP-NP showed average improvements of 0.89 log10 and 1.66 log10 respectively over standard cream counterparts. Dermal toxicity studies were carried out in a rat skin excision model which showed a similar wound healing pattern to that in rats treated with standard cream formulations as represented by reduction in wound size, and increase in wound healing markers.

Main-chain polyacetal conjugates with HIF-1 inhibitors: temperature-responsive, pH-degradable drug delivery vehicles.

Main-chain polymer-drug conjugates are prepared from polyacetals (PA) and three hydrophobic diol-based HIF-1 inhibitors. The new conjugates are temperature-responsive with lower critical solution temperature (LCST) behavior and are intrinsically pH-degradable. While soluble in plasma at room temperature, they lose solubility above a target temperature that can be adjusted to virtually any temperature of physicological interest, providing mechanisms for site-specific delivery by active thermal targeting or temperature-induced gelation. The reverse phase transition temperature can be precisely tuned by proper choice of four structural variables that characterize the amphiphilic diol and divinyl ether monomers used in the synthesis, or by adjusting the content of drug incorporated within the polymer. These main-chain PA-drug conjugates also allow for site-specific controlled release as they degrade in acidic microenvironments such as tumors. The degradation rates increase with decreasing pH, degradation products are neutral, and pristine drug is released, without any remnants of the conjugation chemistry.

Sequence transferable coarse-grained model of amphiphilic copolymers.

Polymer properties are inherently multi-scale in nature, where delicate local interaction details play a key role in describing their global conformational behavior. In this context, deriving coarse-grained (CG) multi-scale models for polymeric liquids is a non-trivial task. Further complexities arise when dealing with copolymer systems with varying microscopic sequences, especially when they are of amphiphilic nature. In this work, we derive a segment-based generic CG model for amphiphilic copolymers consisting of repeat units of hydrophobic (methylene) and hydrophilic (ethylene oxide) monomers. The system is a simulation analogue of polyacetal copolymers [S. Samanta et al., Macromolecules 49, 1858 (2016)]. The CG model is found to be transferable over a wide range of copolymer sequences and also to be consistent with existing experimental data.

Preventing Alkyne-Alkyne (i.e., Glaser) Coupling Associated with the ATRP Synthesis of Alkyne-Functional Polymers/Macromonomers and for Alkynes under Click (i.e., CuAAC) Reaction Conditions.

Alkyne-functional polymers synthesized by ATRP exhibit bimodal molecular weight distributions indicating the occurrence of some undesirable side reaction. By modeling the molecular weight distributions obtained under various reaction conditions, we show that the side reaction is alkyne-alkyne (i.e., Glaser) coupling. Glaser coupling accounts for as much as 20% of the polymer produced, significantly compromising the polymer functionality and undermining the success of subsequent click reactions in which they are used. Glaser coupling does not occur during ATRP but during postpolymerization workup upon first exposure to air. Two strategies are reported that effectively eliminate these coupling reactions without the need for a protecting group for the alkyne-functional initiator: (1) maintaining low temperature post-ATRP upon exposure to air followed by immediate removal of copper catalyst; (2) adding excess reducing agents post-ATRP which prevent the oxidation of Cu(I) catalyst required by the Glaser coupling mechanism. Post-ATRP Glaser coupling was also influenced by the ATRP synthesis ligand used. The order of ligand activity for catalyzing Glaser coupling was: linear bidentate > tridentate > tetradentate. We find that Glaser coupling is not problematic in ARGET-ATRP of alkyne-terminated polymers because a reducing agent is present during polymerization, however the molecular weight distribution is broadened compared to ATRP due to the presence of oxygen. Glaser coupling can also occur for alkynes held under CuAAC reaction conditions but again can be eliminated by adding appropriate reducing agents.