Amphiphilic poly-N-vinylpyrrolidones: synthesis, properties and liposome surface modification

Certain amphiphilic water-soluble polymers including amphiphilic derivative s of polyvinyl pyrrolidone (PVP) were found to be efficient steric protecto rs for liposomes in vivo. In this study, we have tried to develop synthetic pathways for preparing amphiphilic PVP and to investigate the influence of the hydrophilic/hydrophobic blocks on some properties of resulting polymer s and polymer-coated liposomes. To prepare amphiphilic PVP with the end ste aryl (S) or palmityl (P) residues, amino- and carboxy-terminated PVP deriva tives were first synthesized by the free-radical polymerization of vinyl py rrolidone in the presence of amino- or carboxy-mercaptans as chain transfer agents, and then modified by interaction of amino-PVP with stearoyl chlori de or palmitoyl chloride, or by dicyclohexyl carbodiimide coupling of stear ylamine with carboxy-PVP. ESR-spectra of the hydrophobic spin-probe. nitrox yl radical N-oxyl-2-hexyI-2-(10-methoxycarbonyl)decyl-4,4'-dimethyl oxazoli ne, in the presence of amphiphilic PVP demonstrated good accessibility of t erminal P- and S-groups for the interaction with other hydrophobic ligands. Spontaneous micellization and low CMC values (in a low mu molar range) wer e found for amphiphilic PVP derivatives using the pyrene method. In general , S-PVP forms more stable micelles than P-PVP (at similar MW, CMC values fo r S-PVP are lower than for P-PVP). It was found that amphiphilic PVP incorp orated into negatively charged liposomes effectively prevents polycation(po ly-ethylpyridinium-4-vinylchloride)-induced liposome aggregation, completel y abolishing it at ca. 10mol% polymer content in liposomes. Additionally, t he liposome-incorporated PVP prevents the fluorescence quenching of the mem brane-incorporated hydrophobic fluorescent label [N-(4-fluoresceinthiocarba moyl)dipalmitoyl-PE] by the free polycation. PVP-modified liposomes were lo aded with a self-quenching concentration of carboxyfluorescein, and their d estabilization in the presence of mouse serum was investigated following th e release of free dye. Amphiphilic PVP with MW between 1500 and 8000 provid es good steric protection for liposomes. The degree of this protection depe nds on both polymer concentration and molecular size of the PVP block. (C) 2001 Elsevier Science Ltd. All rights reserved.