Modified polypeptides containing gamma-benzyl glutamic acid as drug delivery platforms

We previously reported the development of diffusion-controlled biodegradabl e polypeptides for drug delivery purposes. In this paper, we describe the s ynthesis of three modified polypeptides that contain gamma-benzyl glutamic acid as the common structural backbone. The properties of these polymers we re characterized with regard to their potential application as drug deliver y platforms. Procainamide hydrochloride, a hydrophilic drug, and protamine sulfate, a low molecular weight protein, were used as model drugs for exami ning release rate profiles from these polymers. The homopolymer of poly(gam ma-benzyl-L-glutamic acid), PBLG, showed a highly helical configuration and a moderate release rate of procainamide. Modification of structural attrib utes by random copolymerization of the D- and L- isomers of gamma-benzyl gl utamic acid produced poly(gamma-benzyl-D,L-glutamic acid), PBDLG, which dis played a significantly slower release of procainamide when compared to PBLG . The modification of polymer bulk hydrophobicity by copolymerization of PB LG (A) with poly(ethylene glycol) (B) yielded an ABA triblock copolymer exh ibiting much faster release rates for both procainamide and protamine than those demonstrated by the other two polymers. Using this triblock copolymer , protamine release rates ranging from 2 weeks to approximately 2 months we re obtained by simply varying the polymer processing conditions and protein particle size. A nearly complete release of protein was obtained from the triblock copolymer blends and this occurred without reliance upon degradati on of the polymer backbone. Fickian diffusion-controlled release mechanisms were implied for release of procainamide and protamine from these polypept ide formulations based on the linear relationship displayed between cumulat ive drug release and the square root of time. (C) 1999 Elsevier Science B.V . All rights reserved.