Mannose 6-phosphate-modified bovine serum albumin nanoparticles for controlled and targeted delivery of sodium ferulate for treatment of hepatic fibrosis.
OBJECTIVE
The aim was to prepare neoglycoprotein-based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo.


METHODS
The neoglycoprotein of bovine serum albumin modified with mannose 6-phosphate was synthesised from mannose, and used as wall material to nanoencapsulate the model natural antifibrotic substance sodium ferulate using a desolvation method. The morphology, drug loading capacity, release in vitro and biodistribution in vivo of the nanoparticles were studied. Selectivity of the nanoparticles for hepatic stellate cells was evaluated by immunohistochemical analysis of fibrotic rat liver sections.


RESULTS
The spherical nanoparticles were negatively charged with zeta potential ranging from -2.73 to -35.85 mV, and sizes between 100 and 200 nm with a narrow size distribution. Drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) could be achieved. in vitro, the nanoparticles showed an initial rapid continuous release followed by a slower sustained release. After intravenous injection into mice, the nanoparticles showed a slower elimination rate and a much higher drug concentration in liver compared with the sodium ferrate solution, and less distribution to the kidneys and other tissues. Immunohistochemistry indicated that the neoglycoprotein-based nanoparticles were taken up specifically by hepatic stellate cells.


CONCLUSIONS
The nanoparticles may be an efficient drug carrier targeting hepatic stellate cells.
Li
Feng-Qian
FQ
Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai 200235, China. fqlijr@gmail.com
Su
Hua
H
Chen
Xu
X
Qin
Xian-Ju
XJ
Liu
Ji-Yong
JY
Zhu
Quan-Gang
QG
Hu
Jin-Hong
JH
D000818:Animals; D003373:Coumaric Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D006023:Glycoproteins / Q000008:administration & dosage / Q000138:chemical synthesis; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008360:Mannosephosphates / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution
D003373:Coumaric Acids; D004337:Drug Carriers; D006023:Glycoproteins; D008360:Mannosephosphates; D012710:Serum Albumin, Bovine; C027693:mannose-6-phosphate; C004999:ferulic acid