Dual delivery of chlorhexidine and platelet-derived growth factor-BB for enhanced wound healing and infection control

Abstract

Wound treatment can require molecules that both enhance healing and control infection. As in many biomedical applications, the options for therapeutic molecules may include both hydrophilic and hydrophobic molecules. The goal of this study was to investigate a polymer system for drug delivery that simultaneously delivers platelet-derived growth factor (PDGF)-BB, a hydrophilic protein known to promote wound healing, and chlorhexidine (CHX), a hydrophobic antimicrobial agent for infection treatment. Poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared using different polymer formulations in a double emulsion process. CHX encapsulation efficiency was 19.6±0.8% and 28.9±1.5% for PLGA 50:50 and 85:15, respectively. The presence of CHX significantly increased PDGF-BB encapsulation efficiency relative to PDGF-BB alone. Both molecules could be released for up to 50days and exhibited bioactivity for greater than 3 (PLGA 85:15) or 8 (PLGA 50:50) weeks using in vitro bacteria and cellular assays. An infected wound model was used to evaluate the system in vivo. Wounds treated with the dual delivery system showed decreased levels of infection and increased healing. Vascular analysis of wound tissues also showed higher levels of mature vasculature with the delivery of PDGF-BB. In conclusion, we have evaluated a drug delivery system for simultaneous delivery of hydrophobic and hydrophilic molecules and have shown that this system can improve healing and reduce bacteria levels in an infected wound model. This system could be applied to other therapeutic applications where sustained delivery of hydrophobic and hydrophilic molecules is required.