多西紫杉醇壳聚糖纳米粒制备及其特性研究

Preparation and evaluation of Docetaxel-loaded chitosan nanoparticles in vitro

目的制备负载多西紫杉醇(DTX)的壳聚糖纳米粒(DTX-CTNPs),并研究其体外释药性能及细胞毒性。方法采用离子交联法制备DTX-CTNPs,扫描电镜观察其形态学特征,激光粒度分析仪测定纳米粒粒径大小及分布,在磷酸盐缓冲液(PBS)中对载药纳米粒进行体外释药试验。四甲基偶氮唑盐(MTT)法检测DTX-CTNPs对人肺腺癌细胞株A549的增殖抑制以评估其细胞毒性及抗瘤效应。结果壳聚糖和三聚磷酸钠投药比为5.3∶1.0时制备的壳聚糖纳米粒(CTNPs)形态规则,粒径分布较为均匀,平均粒径为175nm,载药率与包封率分别为(22.4±2.7)%、(59.2±8.6)%。对A549细胞株的体外增殖抑制作用具有浓度依赖性,半数抑制浓度(IC50)为(26.87±1.35)μg/mL,而同一实验体系下的普通注射用DTX的IC50则为(5.51±0.37)μg/mL(P<0.001),证明载药纳米粒的细胞毒性远低于普通注射用DTX。结论 DTX-CTNPs具有一定的控释性能,能明显降低普通注射用DTX的细胞毒性,可以成为一种理想的化疗药载体。

Objective To prepare docetaxel-loaded chitosan nanoparticles（DTX-CTNPs） by optimizing experiment conditions.And the drug-loaded NPs were evaluated for sustain release and in vitro cytotoxicity.Methods DTX-CSNPs were prepared by ionotropic gelation of chitosan with tripolyphosphate anions（TPP）.The NPs were characterized for their shape by scanning electron microscopy.The particle size,size distribution and polydispersity index were assessed by laser scattering.The drug loading,incorporation efficiency and cumulative release rates of the DTX-CTNPs in vitro were analyzed by ultraviolet spectrophotometry.The DTX-CTNPs were evaluated for in vitro cytotoxicity by MTT assay using A549 cell lines.Results The DTX-CTNPs（CTS/TPP 5.3∶1.0） with good shape and narrow size distribution were prepared.The average diameter was 175 nm.The rates of drug loading and encapsulation were（22.4±2.7）% and（59.2±8.6）%,respectively.And the DTX-CTNPs showed a comparable antitumor efficacy in vitro while strongly reduced the anticancer drug toxicity compared to free DTX（DTX for injection）.Conclusion Together our results suggests that the anticancer drug loaded nanoparticles are a promising nano-sized drug vector for cancer therapy.