Preparation, characterization and uptake by primary cultured rat hepatocytes of liposomes surface-modified with glycyrrhetinic acid.
3-succinyl-30-stearyl glycyrrhetinic acid (Suc-GLAOSt) was synthesized as a targeting molecule, and incorporated in ordinary to liposomes (LP) to prepare a liposome surface-modified with glycyrrhetinic acid (LP-GLA), which could bind to the hepatocyte through the specific binding site of glycyrrhetinic acid (GLA) on the surface of rat cellular membrane. The maximal molar ratio of Suc-GLAOSt to total lipids in LP-GLA was 1:10. Calcein loaded liposome (Cal-LP) and calcein loaded LP-GLA (Cal-LP-GLA) were prepared by an ethanol injection method. The average diameter of Cal-LP and Cal-LP-GLA was 65 nm +/- 16 nm and 68 nm +/- 21 nm, respectively. The characteristics of cellular uptake of the two types of liposome were investigated through cellular uptake and competitive inhibition experiments. The uptake of Cal-LP-GLA by rat hepatocytes was markedly higher (3.3-fold) than that of Cal-LP (P < 0.01). The uptake of Cal-LP-GLA was inhibited, but the uptake of Cal-LP was not influenced by adding extraneous GLA. LP-GLA may be internalized by hepatocytes via the specific binding site, and can be used as a novel and promising carrier for targeting drug delivery to hepatocytes.
Mao
Sheng-Jun
SJ
Key Laboratory of Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University Chengdu, PR China.
Bi
Yue-Qi
YQ
Jin
Hui
H
Wei
Da-Peng
DP
He
Ru
R
Hou
Shi-Xiang
SX
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005452:Fluoresceins / Q000737:chemistry; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
D004337:Drug Carriers; D005452:Fluoresceins; D007202:Indicators and Reagents; D008081:Liposomes; D006034:Glycyrrhetinic Acid; C007740:fluorexon