Enlarging the library of poly-(L-lysine citramide) polyelectrolytic drug carriers

Poly-(L-lysine citramide) is a degradable drug carrier of the polyelectroly te type that is composed of citric acid and L-lysine building blocks. In a previous work, poly-(L-lysine citramide) was synthesized by the interfacial polycondensation of a-hydroxy acid protected citryl dichloride with COOH-p rotected lysine diamine. Because of head-to-head and head-to-tail and tail- to-tail linkages in the chains as well as various side reactions such as de protection of the a-hydroxy acid moieties and intramolecular imide ring for mation, a very large family of degradable polyelectrolyte copolymers was ob tained. Ail the members of this family hydrolytically degrade to the same e nd products. In this study, another route was explored based on the polycon densation of a-hydroxy acid protected citric acid pentafluorophenyl diester s, namely, citrobenzal dipentafluorophenyl and citrochloral dipentafluoroph enyl with N-N'-trimethylsilylated COOH-protected L-lysine. The resulting po lymers were characterized by IR, NMR, and size exclusion chromatographic an alyses. The resulting chain structures and repeat units were identified fro m these characterizations and are discussed as compared with characteristic s exhibited by analogous polymers resulting from interfacial polycondensati on. Differences observed at the intermediate stage involving protected poly mers were largely erased during the final deprotection stage because of imi de formation ;during final hydrolysis under the selected conditions. (C) 20 01 John Wiley & Sons, Inc.