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

Abstract

AbstractPoly‐(L‐lysine citramide) is a degradable drug carrier of the polyelectrolyte 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 α‐hydroxy acid protected citryl dichloride with COOH‐protected 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 deprotection of the α‐hydroxy acid moieties and intramolecular imide ring formation, a very large family of degradable polyelectrolyte copolymers was obtained. All the members of this family hydrolytically degrade to the same end products. In this study, another route was explored based on the polycondensation of α‐hydroxy acid protected citric acid pentafluorophenyl diesters, namely, citrobenzal dipentafluorophenyl and citrochloral dipentafluorophenyl with N‐N′‐trimethylsilylated COOH‐protected L‐lysine. The resulting polymers were characterized by IR, NMR, and size exclusion chromatographic analyses. The resulting chain structures and repeat units were identified from these characterizations and are discussed as compared with characteristics exhibited by analogous polymers resulting from interfacial polycondensation. Differences observed at the intermediate stage involving protected polymers were largely erased during the final deprotection stage because of imide formation during final hydrolysis under the selected conditions. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3475–3484, 2001