透明质酸修饰的白蛋白纳米粒的制备及抗肿瘤作用的初步评价

Prepatation of a Hyaluronic Acid Modified Bovine Serum Albumin Nanoparticle and Its Anti-tumor Effect

目的制备透明质酸修饰的白蛋白纳米粒,对其修饰程度和载药性能进行考察,并初步评价其抗肿瘤作用。方法用去溶剂化法制备白蛋白纳米粒,并用透明质酸修饰纳米粒表面,以表面活性氨基的减少作为评价透明质酸修饰的白蛋白纳米粒的修饰程度的指标,并筛选最佳处方;考察pH和载药量及包封率的关系。使用噻唑蓝比色法(MTT)测定纳米粒对人肝癌细胞株HepG2的抑制率。结果制备所得的透明质酸修饰的白蛋白纳米粒的平均粒径为396 nm,Zeta电位-19.7 mV,表面氨基减少率为34.28%;透明质酸修饰的米托蒽醌白蛋白纳米粒载药量11.13%,包封率94.64%,平均粒径为398 nm,Zeta电位-17.9 mV,且具有明显的缓释作用。透明质酸修饰的米托蒽醌白蛋白纳米粒比米托蒽醌水溶液具有更强的细胞抑制率(P<0.05)。结论所用制备工艺稳定,可用于制备透明质酸修饰的白蛋白纳米粒。透明质酸修饰的米托蒽醌白蛋白纳米粒具有不低于药物溶液的活性。

Objective To prepare hyaluronic acid modified bovine serum albumin nanoparticle,investigate the modification extent,the drug entrapment property and its anti-tumor effect.Methods Bovine serum albumin nanoparticles were prepared by desolvation method,then use hyaluronic acid to modify the surface of bovine serum albumin nanoparticle.The decrement of reactive amino groups on the surface of bovine serum albumin nanoparticleswas applied to evaluate the modification extent of hyaluronic acid.Single factor was used to study the effects of several influencing factors in preparation on the modification extent of hyaluronic acid modified bovine serum albumin nanoparticles.The influence of pH on drug entrapment ratio as well as the drug entrapment property were studied.The inhibition rate of nanoparticle on HepG2 was evaluated with MTT asasay.Results The prepared hyaluronic acid modified bovine serum albumin nanoparticle had a average particle size of 396 nm,and Zeta potential of-19.7 mV,the deceased ratio of surface reactive amino groups was 34.28%;hyaluronic acid modified mitoxantrone bovine serum albumin nanoparticles had a property of drug load ratio 11.13%,drug entrapment ratio 94.64% and 398 nm average particle size,Zeta potential-17.9 mV,with a distinguished delayed drug release effect.A higher inhibition rate was observed for hyaluronic acid modified bovine serum albumin nanoparticle than that of mitoxantrone solution（P0.05）.Conclsuion The preparation technique is stable which could be used to prepare hyaluronic acid modified bovine serum albumin nanoparticle,and the prepared nanoparticle has a higer anti-tumor effect than that of mitoxantrone solution.