Novel polylactic acid nanoparticles containing tanshinone IIA (TS-PLA-NPs) were synthesized by a single oil-in-water emulsion/solvent evaporation method. In this study, the optimized nanoparticles were characterized for morphology, mean particle size, zeta potential, entrapment efficiency, drug-loading content, X-ray diffractometer measurement, and in vitro release. The obtained nanoparticles were spherical and intact. The mean particle size was 192.5nm with polydispersity index being 0.029 and zeta potential -26.27mV. The mean entrapment efficiency and loading of tanshinone IIA (TSIIA) in TS-PLA-NPs were 86.35 and 1.61%, respectively. The in vitro release study was performed at pH 7.4 using a dialysis membrane. Without initial burst effect, the TSIIA sustained release from TS-PLA-NPs for more than 7 days. The mean in vitro cumulative release percentage of TSIIA from TS-PLA-NPs vs. time curve fitted well with the Higuchi Equation (Q=2.0365+13.564t1/2, r=0.9950). In pharmacokinetics and tissue distribution studies, the concentrations of TSIIA are higher in hepatoma and lower in blood, heart, kidney, spleen, and lung at 2h after TS-PLA-NPs was administered via caudal vein. TS-PLA-NPs were effective in destroying the human liver cancer cells by the Mono-nuclear cell direct cytotoxicity assay (MTT) assay, and the growth-inhibitory effect of TS-PLA-NPs on human liver cancer cells was concentration and time dependent. The effect of TS-PLA-NPs on hepatoma in mice was also performed. The results of TS-PLA-NPs were markedly more effective than both of TSIIA and blank PLA nanoparticles in preventing tumor growth and increasing survival time of mice with hepatoma. This study provided support for the new paradigm, the application of TSIIA for the treatment of hepatoma.
[1]Shanghai Univ Tradit Chinese, Putuo Hosp, Dept Oncol, Shanghai 200062, Peoples R China.
[2]Shanghai Univ Tradit Chinese, Dept Pharmaceut, Shanghai 200062, Peoples R China.
(8.0+极速模式)