Superhydrophilic zwitterionic polymers stabilize liposomes.
Nonionic polyethylene glycol (PEG) as a stealth polymer destabilizes liposomes due to its amphiphilic property. As a result, PEGylated liposomes have to be further stabilized, such as by using a large amount cholesterol. This is a long existing dilemma faced by PEG. In this work, we show that zwitterionic poly(carboxybetaine) (PCB) stabilizes liposomes because of its superhydrophilic nature, thus solving this dilemma. Specifically, PCB-modified liposomes without cholesterol exhibited good retention of hydrophilic drug and long blood circulating characteristics in vivo. To further validate this new PCB chemistry, PCB liposomal doxorubicin without cholesterol was compared with DOXIL for their antitumor therapeutic efficacies.
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Zhiqiang
Z
Cao
Lei
L
Zhang
Shaoyi
S
Jiang
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001622:Betaine / Q000031:analogs & derivatives*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006207:Half-Life; D057927:Hydrophobic and Hydrophilic Interactions; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; C024098:6-carboxyfluorescein; D001622:Betaine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol