Uptake of albumin nanoparticle surface modified with glycyrrhizin by primary cultured rat hepatocytes.
OBJECTIVE
To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane.


METHODS
Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NP-GL and Cal-BSA-NP by rat hepatocytes was determined by fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL.


RESULTS
Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of Cal-BSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P<0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.


CONCLUSIONS
A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.
Mao
Sheng-Jun
SJ
West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan Province, China.
Hou
Shi-Xiang
SX
He
Ru
R
Zhang
Liang-Ke
LK
Wei
Da-Peng
DP
Bi
Yue-Qi
YQ
Jin
Hui
H
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000493:pharmacokinetics; D005452:Fluoresceins; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D049329:Nanostructures; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000187:drug effects* / Q000493:pharmacokinetics*
D004337:Drug Carriers; D005452:Fluoresceins; D012710:Serum Albumin, Bovine; D019695:Glycyrrhizic Acid; C007740:fluorexon