In vitro and in vivo analysis of antide delivery from multi-phase microspheres fabricated via solvent removal

Antide, a gonadotropin releasing hormone (GnRH) antagonist, has been studied as a new drug for treatment of various gonadotropin-dependent disorders, including hormone-dependent prostate and breast cancer. Antide was encapsulated into multi-phase microspheres composed of poly(L-lactic)acid (PLLA) and poly(fumaric-co-sebacic)anhydride (P(FA:SA)) fabricated via solvent removal and loaded at 5% and 20% (w/w). In vitro release kinetics and the in vivo therapeutic effect (changes in the testosterone levels) were evaluated. In vivo studies were conducted in male rats at a dose of 12.5 mg antide/kg for both the 5% and 20% loaded particles as well as 31.5 mg antide/kg for the 20% loaded particles. The 5% loaded particles achieved a decrease in testosterone levels below the castration level (0.5 ng/mL) over the course of 11 weeks. The 20% loaded particles resulted in testosterone levels below the castration level for 7 weeks. The results of these studies demonstrate that it is possible to encapsulate antide into a controlled delivery system for more than 2 months. Furthermore, we were able to achieve a therapeutic response in vivo indicated by serum testosterone levels below the castration level of 0.5 ng/mL for at least 11 weeks.