Preparation and evaluation of N-caproyl chitosan nanoparticles surface modified with glycyrrhizin for hepatocyte targeting.
BACKGROUND
The development of an efficient targeted drug delivery system into cells is an important subject for the advancement of drug carriers. In this study, a novel hepatocyte-targeted delivery system with glycyrrhizin (GL) surface modification based on N-caproyl chitosan (CCS) has been developed.


METHODS
CCS was synthesized by acylation of amino group of chitosan, and GL was oxidized to be conjugated to the surface of N-caproyl chitosan nanoparticles (CCS-NPs-GL). The synthesized nanoparticles were first characterized for their morphology, particle size, zeta potential, in vitro stability in plasma, tissue distribution, and hepatocyte-targeting uptake in vivo.


RESULTS
The obtained results showed that the spherical and discrete nanoparticles prepared with oxidized GL/CCS ratio of 0.14:1 (w/w) exhibited a positive electrical charge and associated adriamycin quite efficiently (association efficiency: 87.5%). The prepared nanoparticles also possessed dimensional and GL surface-binding stability and slow release property in plasma in vitro. The biodistribution of these particles after intravenous injections in mice revealed accumulating drug concentrations in the liver, spleen, and lungs while decreasing drug concentrations in the heart and kidney. The content of adriamycin-loaded CCS-NPs-GL in the liver was 1.6 times higher than that of non-GL-modified CCS-NPs. Furthermore, in vivo uptake of CCS-NPs-GL by rat hepatocytes showed 2.1 times higher nanoparticle uptake compared with non-GL-modified CCS-NPs, which suggested that CCS-NPs-GL were preferentially distributed in hepatocytes by a ligand-receptor interaction.


CONCLUSIONS
This article indicated that CCS-NPs-GL was a stable and effective drug delivery vehicle for hepatocyte targeting.
Lin
AiHua
A
Pharmaceutics Laboratory of TCM, The Second Faculty of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China. linah76@163.com
Chen
Jun
J
Liu
YiMing
Y
Deng
Shigui
S
Wu
Zhifeng
Z
Huang
Yu
Y
Ping
QiNeng
Q
D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005434:Flow Cytometry; D019695:Glycyrrhizic Acid / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism*; D007275:Injections, Intravenous; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014018:Tissue Distribution
D004337:Drug Carriers; D019695:Glycyrrhizic Acid; D004317:Doxorubicin; D048271:Chitosan