Synthesis, reactivity, and pH-responsive assembly of new double hydrophilic block copolymers of carboxymethyldextran and poly(ethylene glycol)

Abstract

Double hydrophilic block copolymers (DHBC) were prepared by end-to-end coupling of two biocompatible water-soluble homopolymers: the polysaccharide dextran (Mw 8300 or 14,700 g mol-1) and ω-amino poly(ethylene glycol) (PEG-NH2, Mw 3000 or 7000 g mol-1). The synthesis involved, first, specific oxidation of the dextran terminal aldehyde group and, second, covalent linkage of PEG-NH2 via a lactone aminolysis reaction. The diblock copolymers dextran-PEG (DEX-PEG) were converted in high yield into the corresponding carboxymethyldextran-PEG (CMD-PEG) derivatives with control over the degree of substitution, from 30 to 85 mol% CH2COOH groups per glucopyranosyl unit. Further modifications of a CMD-PEG block copolymer led to N-(2-aminoethyl)carbamidomethyldextran-PEG yielding a pair of oppositely-charged DHBC of identical charge density, chain length, and neutral block/charged block content. The properties of CMD-PEG in aqueous solutions were studied by static and dynamic light scattering as a function of solution pH, providing evidence of the pH-sensitive assembly of the copolymers driven by inter- and intra-chain hydrogen-bond formation. © 2006 Elsevier Ltd. All rights reserved.