ANALYSIS OF THE INFLUENCE OF POLYMER CHARACTERISTICS AND CORE LOADINGON THE IN-VIVO RELEASE OF A SOMATOSTATIN ANALOG

Peptides and proteins have received much attention in recent years as candidate drugs. Vapreotide (RC-160) is a somatostatin analogue used f or the therapy of hormone-dependent tumors and endocrine disorders. Li ke other peptides, it cannot be administered by the oral route and its plasma half-life is relatively short after parenteral administration. For these reasons, its use would be greatly enhanced by a sustained d elivery system capable of maintaining controlled plasma levels of the peptide over an extended period of time. Poly(D,L-lactide-co-glycolide ) (PLGA) are biocompatible biodegradable materials useful for a variet y of applications, including the design of controlled-release systems for pharmaceutical agents. RC-160 pamoate loaded implants are proposed in this work as a means for controlling the drug release. Various PLG A were studied as biodegradable drug carriers and their in vivo releas e profiles were examined. Poly(D,L-lactide-co-glycolide) implants cont aining RC-160 were prepared by an extrusion method and the drug releas e was evaluated in vivo in rats using a radioimmunoassay method. The e ffects on the release profile, obtained by varying molecular weight, l actide/glycolide ratio and core loading were studied. The effects of p olymer end groups were also investigated. Gel permeation chromatograph y was employed to characterize the loss in molecular weight of the dif ferent polymers after extrusion and gamma-sterilization. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vivo r elease properties. However, even though complex problems still exist, controlled release of peptides from biodegradable PLGA matrices can be achieved.