蛇床子素-pH敏感型纳米粒的制备及其抗肿瘤活性的研究

Studies on Preparation and Anti-tumor Activities of pH-sensitive Osthol-Nanoparticles

目的:制备蛇床子素-Eudragit S100-pH敏感型纳米粒(Ost-S100-NP),并考察Ost-S100-NP体内和体外的抗肿瘤活性。方法:以乳化-溶剂扩散法制备Ost-S100-NP胶体溶液,体外采用MTT法考察Ost和Ost-S100-NP对宫颈癌细胞Hela-3的抑制作用;体内Ost对小鼠宫颈癌U14实体瘤的抗肿瘤试验采用常规的抗肿瘤试验方法,考察不同给药浓度、不同剂型对小鼠体质重、肿瘤生长和胸腺、脾及肝等脏器质量变化的影响。结果:Ost体外对Hela-3细胞的半数抑制浓度IC50分别为:61.25,56.87,48.46μg/mL;Ost-S100-NP的IC50则分别为46.57,40.23,37.46μg/mL;体内Ost及其Ost-S100-NP制剂对荷瘤小鼠的实体瘤抑制率最高可达40%,各给药组与空白对照组比较,差异有统计学意义(P<0.01)。结论:Ost-S100-NP体外和体内均有明显的抗肿瘤活性,且在治疗剂量下未出现毒性反应,有望开发成1种高效、低毒的Ost-S100-NP制剂。

Objective： To prepare Osthol-Eudragit S100-nanoparticles （Ost-S100-NP） and to study on its anti-tumor activities in vitro and in vivo. Methods： Ost-S100-NP were prepared by emulsion-solvent diffusion method. In vitro, antitumor assay was performed by Hela-3,MTT method was employed, and half-inhibitory concentrations （IC50） were recorded. In vivo, the mice cervical cancer（U14） was selected and conventional assay method was employed. Osthole was administered by P.O .way. Tumor inhibitory percentage, thymus gland,spleen indexes and liver weight were measured. Results： IC50 of osthole in U14 was 61.25, 56.87 and 48.46 μg/mL, IC50 of Ost-S100-NP was 46.57, 40.23 and 37.46 μg/mL. In vivo, tumor inhibitory was top to 40%, all treated groups compared with control animals revealed statistical significance（P0.01）. Conclusion： Ost-S100-NP had obvious anti-tumor activities in vitro and in vivo, and did not dispiay any toxic effects in experimental animals at the administered doses. It is a potential carriermaterial in developing a high performance Ost-nanometer system with low toxicity.