地高辛-PLGA抗肿瘤纳米粒子的制备及其抗肿瘤活性的初步研究

Preparation of digoxin loaded PLGA nanoparticles and its inhibition of tumor growth and metastasis

目的 制备载地高辛的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒子,提高地高辛的生物利用度,降低其毒副作用.方法 建立测定地高辛-PLGA纳米粒子载药量和包封率的高效液相色谱法;采用乳化溶剂挥发法制备地高辛-PLGA纳米粒子,并通过单因素实验优化制备条件;采用噻唑蓝法评价地高辛和地高辛-PLGA纳米粒子的抗肿瘤能力.结果 以粒径为筛选条件的单因素实验结果表明,制备地高辛-PLGA纳米粒子的最佳条件为PLGA 30 mg,地高辛2 mg,二氯甲烷3 ml,聚乙烯醇质量分数0.5％,超声功率200 W.此制备条件下得到的地高辛-PLGA纳米粒子的粒径约231 nm,包封率为74.61％,载药量为5.37％,且其抗肿瘤活性优于地高辛,差异具有统计学意义（P＜0.05）.结论 以PLGA为载体材料制备地高辛-PLGA纳米粒子可增强地高辛的抗肿瘤作用.

Ohjective To prepare digoxin loaded poly（lactic-co-glycolic acid） （PLGA） nanoparticles,so as to improve bioavailability and reduce toxic side effects of digoxin.Methods The approach for determining loading capacity and encapsulating efficiency of digoxin-PLGA nanoparticles was established based on high-performance liquid chromatography method.The digoxin-PLGA nanoparticles were prepared by emulsion solvent evaporation method.The preparation conditions were optimized by single factor experiments.The antitumor activities of digoxin and the digoxin-PLGA nanoparticles were assessed by methyl thiazol tetrazolium （MTT） assay.Results The results of single factor experiments indicated that the optimal condition,with the standard of particle size,is as follow：PLGA 30 mg,digoxin 2 mg,dichloromethane 3 ml,polyvinyl alcohol 0.5%,and ultrasound power 200 W.By using the optimal condition,the diameter of the prepared digoxin-PLGA nanoparticles was approximately 231 nm,and the drug loading capacity and encapsulating efficiency of digoxin were 74.61% and 5.37% respectively.It was found that the anticancer activity of the digoxin-PLGA nanoparticles was higher than that of digoxin.Conclusions The digoxin-PLGA nanoparticles,prepared with PLGA as drug delivery material,can enhance the anti-tumor effect of digoxin.