PMID- 7918551 OWN - NLM STAT- MEDLINE DCOM- 19941121 LR - 20190610 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1195 IP - 1 DP - 1994 Oct 12 TI - Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity. PG - 11-20 AB - The hypothetical model is built explaining the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo. The protective layer of the polymer on the liposome surface is considered as a statistical 'cloud' of polymer possible conformations in solution. Computer simulation was used to demonstrate that relatively a small number of liposome-grafted molecules of hydrophilic and flexible polymer can create a dense protective conformational cloud over the liposome surface preventing opsonizing protein molecules from contacting liposome. A more rigid polymer fails to form this dense protective cloud, even when hydrophilic. Computer simulation was also used to reveal possible heterogeneity of reactive sites on a polymer-coated liposome surface, and to estimate the optimal polymer-to-lipid ratio for efficient liposome protection. Experiments have been performed with the quenching of liposome-associated fluorescent label (nitrobenzoxadiazole or fluorescein) with protein (rhodamine-ovalbumin or anti-fluorescein antibody) from solution. It was shown that poly(ethylene glycol) grafting to liposomes hinders protein interaction with the liposome surface, whereas liposome-grafted dextran (more rigid polymer) in similar quantities does not affect protein-liposome interaction. Highly-reactive and low-reactive populations of chemically identical reactive sites have been found on polymer-coated liposomes. Experimental data satisfactory confirm the suggested mechanism for the longevity of polymer-modified liposome. FAU - Torchilin, V P AU - Torchilin VP AD - Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital-East, Charlestown 02129. FAU - Omelyanenko, V G AU - Omelyanenko VG FAU - Papisov, M I AU - Papisov MI FAU - Bogdanov, A A Jr AU - Bogdanov AA Jr FAU - Trubetskoy, V S AU - Trubetskoy VS FAU - Herron, J N AU - Herron JN FAU - Gentry, C A AU - Gentry CA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Fluorescent Dyes) RN - 0 (Liposomes) RN - 0 (Polymers) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Binding Sites MH - Computer Simulation MH - Drug Stability MH - Fluorescent Dyes MH - Liposomes/*chemistry MH - Molecular Conformation MH - Polyethylene Glycols/*analysis MH - Polymers/*chemistry MH - Surface Properties EDAT- 1994/10/12 00:00 MHDA- 2001/03/28 10:01 CRDT- 1994/10/12 00:00 PHST- 1994/10/12 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1994/10/12 00:00 [entrez] AID - 0005-2736(94)90003-5 [pii] AID - 10.1016/0005-2736(94)90003-5 [doi] PST - ppublish SO - Biochim Biophys Acta. 1994 Oct 12;1195(1):11-20. doi: 10.1016/0005-2736(94)90003-5.