Preparation of long-circulating immunoliposomes containing adriamycin by a novel method to coat immunoliposomes with poly(ethylene glycol).
Modifications of liposomes with poly (ethylene glycol) (PEG) have been reported to prolong blood circulation time of liposomes. In this report, an adriamycin-encapsulated immunoliposomes were modified with PEG by two different approaches: one is the pre-coating method using lipid derivative of PEG as described by Allen et al. The other is post-coating method which is presented here. The former pre-coating method did not allow coupling of antibody due to the steric hindrance of PEG which had been introduced on liposome surface. On the other hand, in the later post-coating method, PEG-succinylcysteine was synthesized and was successfully conjugated with immunoliposomes via maleimido linker. Resultant PEG-coated immunoliposomes containing adriamycin retained their binding activity and cytotoxicity to target cells, and also showed significantly prolonged blood circulating time as compared with conventional immunoliposomes. This is a novel method to coat immunoliposomes with PEG.
Suzuki
S
S
Department of Hygienic Chemistry, Faculty of pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Watanabe
S
S
Masuko
T
T
Hashimoto
Y
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage*; D006207:Half-Life; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis* / Q000276:immunology / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols
D000906:Antibodies; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin