Cholesterol as a bilayer anchor for PEGylation and targeting ligand in folate-receptor-targeted liposomes.

Abstract:

: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.

journal_name

J Pharm Sci

authors

Zhao XB,Muthusamy N,Byrd JC,Lee RJ

doi

10.1002/jps.20885

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

2424-35

issue

9

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)32340-1

journal_volume

96

pub_type

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