BIODEGRADABLE POLYMER SYSTEMS FOR THE SUSTAINED-RELEASE OF POLYPEPTIDES

In order to develop delivery systems for polypeptides based on biodegradable polymers, it is necessary to consider fully the physicochemical properties of the macromolecular drug. These include its molecular size and structure as well as the drug-polymer interactions with the polymeric membrane or matrix which is intended to modulate release. This is particularly true for sustained delivery systems based on homo- and co-polymers of lactic and glycolic acids. The physkochemical properties of polypeptides and proteins are such that partition-dependent diffusional transport through the essentially hydrophobic, biodegradable polyester phase cannot occur. However we have shown that continuous release of these macromolecular drugs over weeks or even months can be achieved by controlling the morphology of the drug-polymer mixture and by using polymers whose degradation characteristics can be manipulated. It has been demonstrated that the degradation of the polyesters is characterised by a decreasing molecular weight and an increased uptake of water as degradation proceeds, generation of microporosity and weight loss or erosion. The principal parameters controlling degradation are (co-)polyester composition, polymer structure with regard to the distribution and segmental length of co-monomer units in co-polymers, and the polymer molecular weight and its distribution. Emphasis has focused on the design of biodegradable polymers for the continuous release of Zoladexa goserelin, ICI (118630); d-Ser (But)6Azgly 10-LHRH], which is a highly potent synthetic analogue of luteinizing hormone-releasing hormone (LHRH). However, it has been shown that the technology can be applied to other polypeptides and proteins. © 1990.