Development of biodegradable chlorhexidine-functionalized polyurethane nanofibers for antimicrobial applications

Abstract

Conventional chlorhexidine (CHX) formulations provide a short-term antibacterial effect which necessitates repeated application with compromised patient compliance. There is an unmet demand for controlling CHX delivery at local infections or operative sites to comply with specific therapeutic needs. We propose herein CHX-functionalized nanofibers (NFs) fabricated using a series of poly(ethylene glycol)-poly(caprolactone) (PEGCL) amphiphilic copolymers with different molecular weight (MW) and hydrophilicity as an approach to sustaining CHX release. Physicochemical characterization indicated poly(ether-ester-urethane) structures with different MW (85450-338400), relatively high water uptake capacity (150-230 % at 6 h), biodegradability, and cytocompatibility. Electrospinning of organic copolymer solutions containing 0.5 % CHX resulted in NFs with a 263-205 nm mean diameter, 77.3-85.4 % entrapment efficiency, and molecular drug distribution with no discernible drug-copolymer interaction. Drug release from NFs at pH 7.4 and pH 4.5 took place according to different patterns depending mainly on the copolymer MW, hydrophilicity, and content of the PEG segment as well as the medium pH. Multi-hour to multi-day CHX release could be achieved featuring a range of burst and sustained release phases to meet antimicrobial needs ranging from immediate short-term effects at higher drug concentrations to sustained antimicrobial effects in longer-term applications.