Extended release peptide delivery systems through the use of PLGA microsphere combinations

The purpose of this study was to evaluate the utility of combining polymer matrices to overcome extended lag periods or unacceptably short durations o f action intrinsic in the individual polymer systems, Leuprolide, an LHRH s uperagonist, was incorporated into a variety of poly(lactide-co-glycolide) (PLGA) matrices using a solvent extraction/evaporation method. The in vitro release of Leuprolide from these matrices was evaluated at pH 7.0 and 37 d egrees C in phosphate buffer. The formulations were administered to an anim al model at 3 or 9 mg kg(-1) doses and serum testosterone levels were follo wed using a RIA method. A two-part system was made by combining microsphere s made from a 75:25 acid terminated PLGA and microspheres made from a 75:25 ester terminated PLGA. This combination elicited chemical castration from 10-100 days. A three-par? combination composed of an ester terminated 75:25 PLGA formulation, an ester terminated 50:50 PLGA formulation and an acid t erminated 50:50 PLGA formulation also provided a composite profile with an onset of 10 days and a duration of similar to 100 days. Additionally, a sin gle polymer system composed of a high molecular weight ester terminated 75: 25 PLGA was employed to produce release over the desired 90-day release per iod. This study demonstrates that microsphere combinations can potentially provide effective therapies over extended intervals when combined at the pr oper ratio.