Preparation of Curcumin Solid Lipid Nanoparticle and Studies on Its Anti- Cancer Effect and Pharmacokinetics in Rats

摘要

Purpose: The aim of this study was to encapsulate curcumin into solid lipid nanoparticle (SLN) to improve its aqueous solubility and stability, as well as to modify its anti-cancer activity and pharmacokinetics. Methods: Curcumin-loaded SLNs (CSLN) were prepared by high-pressure homogenization. Morphology, physiochemical stability and release profile of curcumin in the optimized formulation were investigated. The anti-cancer activity and intracellular uptake were evaluated on MCF-7 breast cancer cell by SRB and flow cytometry analysis. The pharmacokinetic profiles of curcumin in SLN after intravenous administration were studied in rats. Results: An optimized formulation consisting of Dynasan 114?, Sefso1-218?, Pluronic F68? and curcumin (630:70:300:8,w/w) and loaded with 0.8% drug were prepared, which could dispersed into water with a mean particle size of 152.8 ± 4.7 nm and high entrapment efficiency (~ 90%). Curcumin showed a two-phase sustained release profile from C-SLN with improved chemical stability. C-SLN exhibited a prolonged inhibition activity to cancer cells, which was close to curcumin solubilized solution. A time- dependent increased intracellular uptake of curcumin was observed for C-SLN. Following intravenous administration to rats, both bioavailability and clearance of curcumin increased by 1.25-fold compared with unformulated drug. Conclusion: C-SLN with improved dispensability and chemical stability in aqueous system has been successfully developed. Compared to unformulated drug, C-SLN exhibited a prolonged inhibition to breast cancer cell in vitro and significant higher plasma concentrations in rats after intravenous administration.