Self-assembly and characterization of Pluronic P105 micelles for liver-targeted delivery of silybin.
Polymeric micelles, based on lactobionic acid (LA)-conjugated Pluronic P105 (P105), were prepared to achieve liver-targeted delivery of silybin. In the triblock copolymer structure of PEO-PPO-PEO, LA was successfully conjugated with the terminal end of PEO to produce LA-P105. The success of synthesis was confirmed using FTIR and 1H NMR. The triblock copolymers with functional moiety were physically mixed with silybin to form micelles. Silybin-loaded LA-P105 micelles characterized by dynamic light scattering and transmission electron microscopy (TEM) were uniform spherical particles. There was a remarkable increase in the dissolubility for silybin in LA-P105 micelle solution (627 microg/mL) when compared with that for water (4.6 microg/mL). The pharmacokinetic experiments showed that the area under the curve of silybin plasma concentration-time profile in rats for LA-P105 micelles was lower than that for P105 micelles. Biodistribution studies indicated that a significantly increased amount of silybin was accumulated in liver, suggesting that LA locating on the surface of the micelles played an important role in transporting an increased amount of silybin into liver. This polymeric vehicle is, therefore, expected to be widely used as target-specific delivery vehicles for diverse water-insoluble therapeutic and diagnostic agents.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Xinru
X
Li
Yanqing
Y
Huang
Xingwei
X
Chen
Yanxia
Y
Zhou
Yanhui
Y
Zhang
Pingzhu
P
Li
Yan
Y
Liu
Yufeng
Y
Sun
Jieyu
J
Zhao
Fei
F
Wang
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D004187:Disaccharides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D008027:Light; D008099:Liver / Q000378:metabolism; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D014018:Tissue Distribution
D000975:Antioxidants; D004187:Disaccharides; D004337:Drug Carriers; D008823:Micelles; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D012838:Silymarin; D020442:Poloxamer; D011092:Polyethylene Glycols; D000077385:Silybin; C005608:lactobionic acid; C519610:pluronic P105