WATER-SOLUBLE POLYAMIDES AS POTENTIAL-DRUG CARRIERS .9. POLYASPARTAMIDES GRAFTED WITH AMINE-TERMINATED POLY(ETHYLENE OXIDE) CHAINS

The synthesis of side-chain-functionalized polyaspartamides as potenti al carrier polymers for medicinal agents is described. The nucleophili c ring opening in poly-D,L-succinimide, mediated by O,O'-bis(2-aminopr opyl)poly(ethylene oxide) (nominal molecular mass is 600) and ethanola mine under carefully controlled experimental conditions leads to the f ormation of aspartamide polymers bearing hydrosolubilizing hydroxyethy l side groups in addition to variable proportions of poly(ethylene oxi de) (PEO) side chains terminated with primary amino groups. The side c hain terminals represent functionalities for drug binding, whereas the PEO constituents contribute to overall hydrophilicity and biocompatib ility of the carriers and to enhance their biomedical performance by i mparting resistance to protein binding and increasing central circulat ion lifetime. The water soluble polymeric products are isolated by dia lysis (molecular mass cutoff: 25,000) and freeze-drying in typical yie lds of 40-60%, with inherent viscosities in the range of 10-18 mL g(-1 ). Polymer compositions are determined by H-1 NMR spectroscopy and mic roanalysis. A selected carrier is modified by N-acylation with 4-ferro cenylbutanoic acid as a model drug, giving a ferrocene-containing, wat er-soluble conjugate, thus demonstrating the accessibility of the term inal amino groups on the PEO side chains to acylating agents and other potential reactants. (C) 1997 John Wiley & Sons, Inc.