Characterization of polymeric poly(epsilon-caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids

Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been encapsulated with poly(epsilon-caprolactone) (PCL) microspheres using a w / o /w double emulsion method. The microspheres prepared were smooth and spherical, with a mean size from 8-25 microm. In vitro release profiles of microspheres showed a trend of increasing initially at the first week, and thereafter the release was sustained. At the end of the seventh week LNG/EE from 1:5 and 1:10 PCL microspheres were 60 and 48%, 52 and 46%, respectively. An in vitro degradation study shows that at the 20th week the microspheres maintained the surface integrity. The PCL microspheres showed a triphasic in vivo release profile with an initial burst effect due to the release of the steroid adsorbed on the microsphere surface, a second sustained release phase due to the steroid diffusion through the pores or channels formed in the polymer matrix, and third phase due to polymer bioerodible. Histological examination of PCL microspheres injected intramuscularly into thigh muscle of a rat showed a minimal inflammatory reaction demonstrating that contraceptive steroid-loaded microspheres were biocompatible. The level of inflammatory cytokines determined by immunostaining for IL-1alpha, the tissue response to formulations at the first week was considered mild, whereas at the end of the 20th week the inflammatory response ceased. Thus, this study helped us to evaluate the feasibility of using these microspheres as a long-acting biodegradable drug delivery system for contraceptive steroids.