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 of action intrinsic in the individual polymer systems. Leuprolide, an LHRH superagonist, 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 degrees C in phosphate buffer. The formulations were administered to an animal model at 3 or 9 mg kg(-1) doses and serum testosterone levels were followed using a RIA method. A two-part system was made by combining microspheres 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-part combination composed of an ester terminated 75:25 PLGA formulation, an ester terminated 50:50 PLGA formulation and an acid terminated 50:50 PLGA formulation also provided a composite profile with an onset of 10 days and a duration of approximately 100 days. Additionally, a single polymer system composed of a high molecular weight ester terminated 75:25 PLGA was employed to produce release over the desired 90-day release period. This study demonstrates that microsphere combinations can potentially provide effective therapies over extended intervals when combined at the proper ratio.