Polylactide nanofibers delivering doxycycline for chronic wound treatment

Chronic wounds are of high incidence, difficult to heal, and can cause serious consequences if not properly treated. Doxycycline (DCH) is a broad-spectrum antibiotic and matrix metalloproteinases inhibitor, which has prominent efficacy for chronic wound treatment. Topical DCH treatment is the common administration route for chronic wounds in clinic but may result in low therapeutic efficacy and cause skin irritation at high DCH concentration, since it is difficult to control local drug concentration in the wounds and maintain the effective DCH concentration for a long time. In this study, we prepared DCH-encapsulated polylactide (DCH/PLA) nanofibers by a simple electrospinning method. Imaging studies showed that smooth and continuous DCH/PLA nanofibers with homogeneous DCH distribution were obtained at varied DCH loading content in the range of 5-30%. Mechanical property, water vapour permeability and absorbency of these nanofibers could meet the requirement as wound dressings. By adjusting DCH loading content, the wettability of the nanofibers could be transferred from hydrophobic to hydrophilic, and the release rate of DCH could be controlled in a sustained manner from three days to two weeks. Results of cytotoxicity and antibacterial test indicated that DCH/PLA nanofibers showed good cytocompatibility to L929 mouse fibroblast cells and exhibited positive antibacterial activity against Escherichia coli, suggesting its ability to treat/prevent infectious wounds. For full-thickness wound treatment of diabetic rats, DCH/PLA nanofiber mats can speed up wound healing to a higher extent than topical DCH treatment, due to the sustained release of DCH with less side effects. Our results indicate that DCH/PLA nanofiber mats hold great potential as wound dressings for chronic wound treatment.