Polypeptides for controlled release applications: Synthesis and preliminary characterization and release studies

Abstract

The objective of this study is to evaluate the feasibility of synthesizing biodegradable polypeptide polymers of sufficient hydrophobicity so that release of solute is diffusion controlled. The benefit of such a diffusion-controlled, biodegradable polypeptide system is that the main advantages of biodegradable (avoiding the retrieval of the implanted device) and non-degradable polymers (greater structural integrity) are both exploited. In this study, one sequential polypeptide and two random co-polypeptides with different hydrophobicities were synthesized using active ester intermediates. The polymers were characterized with regard to their chemical composition, molecular weight and hydrophobicity. The in vitro release of a model steroid, 17 α-ethynylestradiol, from compressed disks of these polymers followed a square root of time dependence indicating a diffusion controlled release mechanism. The drug release rates could be varied over several orders of magnitude and covered the therapeutic range for an implantable device delivering the steroid drug on the order of 10 mg per day. The results of these studies indicate that polypeptide co-polymers can be made with sufficient hydrophobicity to provide release rates in the therapeutic range for parenteral drug delivery.