Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation

Abstract

Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation.