Combined Matrix Concept in Delivery of Bioactive Polypeptides

Generally, a polymer implant may release a drug by diffusion at the same time with dissolution of the polymer component without depolymerization (Type A) or by erosion involving depolymerization (Type B). The Type A material induces immune response while the Type B polymer may lead to toxicity problems. It is proposed that a combination of the two types of polymer may attenuate the intensity of the biological responses, because the presence of one in an implant of the same weight reduces the amount of the other. However, it is important to know if sustained delivery may be achieved by such an implant. In this study, partially hydrolyzed poly(vinyl acetate) (PVA) and polycaprolactone (PCL) were chosen as the model Type A. and B polymers, respectively, to evaluate this objective first in vitro with methylene blue (MB) as a model drug. Results show that sustained delivery can be effected, but PCL erosion did not occur as intended. Therefore, PCL served only as a passive component of the implant. while PVA was eroded with the release of MB. Consequently, it was inferred that a polymer may not be required as a passive component. Tests with insulin in a compressed solid admixture with palmitic acid showed that reduction of hyperglycemia in diabetic Wistar rat could be effected repro-ducibly for at least 5 weeks. Thus, the present study, originally planned to test a proposed concept, indicates that non-polymeric materials of known biocompatibility may be suitable for delivery of many bioactive polypeptides as well.