Cholesterol as a bilayer anchor for PEGylation and targeting ligand in folate-receptor-targeted liposomes.
Phospholipids have been extensively evaluated as an anchor for both PEGylation and receptor-targeting in liposomal formulations. However, cholesterol, another important component in biomembranes, has not been fully investigated as an alternative anchor. In this study, the potential role of cholesterol for anchoring PEG and folate was investigated. Cholesterol derivatives were synthesized for PEGylation (mPEG-cholesterol) and folate receptor (FR) targeting (folate-PEG-cholesterol) and incorporated into the bilayer of FR-targeted liposomal doxorubicin. The colloidal stability of these cholesterol derivative-containing liposomes was superior to non-PEGylated liposomes, indicating that steric barrier provided by mPEG-cholesterol can efficiently inhibit aggregation of liposomes. FR-targeting activity of these liposomes was demonstrated by in vitro cell-binding studies on FR-overexpressing KB cells. In addition, in vivo circulation of cholesterol-anchored liposomes was prolonged compared to non-PEGylated liposomes. These studies suggest that cholesterol is a viable bilayer anchor for synthesis of PEGylated and FR-targeted liposomes.
Zhao
Xiaobin B
XB
Division of Pharmaceutics, NCI OSU Comprehensive Cancer Center, NSF Nanoscales Science and Engineering Center (NSEC), College of Pharmacy, The Ohio State University, 542 LM Parks Hall, 500 W. 12th Ave, Columbus, Ohio 43210, USA.
Muthusamy
Natarajan
N
Byrd
John C
JC
Lee
Robert J
RJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D002352:Carrier Proteins / Q000187:drug effects*; D002784:Cholesterol / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004355:Drug Stability; D004655:Emulsions; D005452:Fluoresceins / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007202:Indicators and Reagents; D007624:KB Cells; D007700:Kinetics; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D017785:Photons; D011092:Polyethylene Glycols / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012995:Solubility; D013057:Spectrum Analysis
D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D003692:Delayed-Action Preparations; D004655:Emulsions; D005452:Fluoresceins; D058973:Folate Receptors, GPI-Anchored; D007202:Indicators and Reagents; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol; C007740:fluorexon