Ultrafast and fast bioerodible electrospun fiber mats for topical delivery of a hydrophilic peptide

Abstract

Biodegradable polymers that provide localized controlled delivery of therapeutics within hours to days may have an impact on the topical treatment of skin burns. Here we report for the first time the utility of tyrosine-derived polycarbonate terpolymer electrospun fiber mats as tunable drug delivery matrices. “Ultrafast” (<24h) and “fast”-eroding (<7days) terpolymers were identified. The degradation kinetics of both terpolymers was similar (<20% of initial molecular weight after 7days), while erosion was significantly different (<1 and 4days for ultrafast and fast fibers, respectively). To assess the delivery kinetics, a hydrophilic peptide (P12) was incorporated into the fibers as a model drug. The tunability of polymer composition and its control over release kinetics resulted in significantly different P12 delivery timeframes: total of 9h (“ultrafast” via polymer erosion) and 4days (“fast” via diffusion). The biocompatibility of these fibers was confirmed in a porcine excisional wound model by the (i) lack of inflammatory response to the terpolymers and their degradation products, and (ii) normal progression of healing evaluated for 28days. These results suggest that electrospun tyrosine-derived fibers offer the potential for topical therapies that require ultrafast or fast dose-controlled delivery of the therapeutic.