title: Enhanced circulation time and antitumor activity of doxorubicin by comblike polymer-incorporated liposomes.
abstract: Polymer incorporation on liposomal membranes has been extensively studied as a method of enhancing the circulation time of liposomes in the bloodstream. In this study, we investigated the in vitro and in vivo characteristics of liposomes whose surface was modified using a comblike polymer comprised of a poly(methyl methacrylate) (PMMA) backbone and short poly(ethylene oxide) (PEO) side chains. Doxorubicin (DOX)-loaded liposomes incorporating with the comblike polymer were prepared and their circulation time, biodistribution and antitumor activity were evaluated in B16F10 melanoma tumor-bearing mice. The circulation half-life time in the bloodstream of the comblike polymer-incorporated liposomes (CPILs) was approximately 14- or 2-fold higher than those of the conventional or polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. Additionally, in the biodistribution assay, the accumulation of the CPILs in the tumor was higher than those of the other liposomes. Based on this result, the antitumor activities of the CPILs were higher than those of conventional liposome formulation of DOX or free DOX due to the higher passive targeting efficiency of the long-circulating CPILs to tumor. This study suggests that the incorporation of the comblike polymer on the liposomal membrane is a promising tool to further improve circulation time of liposomes in tumor-bearing mice.
authors.affiliation: Bioactive Molecules Delivery and Control Research Team, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, South Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Aeri
authors.initials: A
authors.lastname: Lee
authors.forename: Taewon
authors.initials: T
authors.lastname: Hwang
authors.forename: Chung Kil
authors.initials: CK
authors.lastname: Song
authors.forename: Hasoo
authors.initials: H
authors.lastname: Seong
authors.forename: Jinho
authors.initials: J
authors.lastname: Hyun
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D011108:Polymers; D004317:Doxorubicin