目的 制备溴化双十二烷基二甲基铵(DMAB)修饰的载汉防己甲素(Tet)的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒(DMAB-Tet-PLGA-NPs),考察其制备的影响因素,优化制备工艺,并对其理化性质、细胞毒性及细胞摄取进行研究。方法 采用乳化分散溶剂挥发法制备DMAB-Tet-PLGA-NPs,运用均匀设计试验优化制备工艺,通过包封率、载药量、累积释药量等指标考察其载药特性;采用MTT比色法考察DMAB-Tet-PLGA-NPs对人肺腺癌细胞株A549的细胞毒性;采用定量定性法评价DMAB-Tet-PLGA-NPs细胞摄取率。结果 制备的DMAB-Tet-PLGA-NPs平均粒径为(205.40±2.66)nm,表面带正电,呈规则的球形及椭圆形。药物包封率和载药量分别为(50.780±3.253)%和(2.130±0.035)%。体外释放实验显示DMAB-Tet-PLGA-NPs缓慢释药,48 h累积释药量64.56%。MTT实验表明DMAB-Tet-PLGA-NPs细胞毒性呈剂量及时间依赖性。定性定量细胞摄取实验证实DMAB-Tet-PLGA-NPs能较好地被细胞摄取。结论 DMAB-Tet-PLGA-NPs粒径大小均一,包封率高,体外释药表现出较好的缓释效果,易被细胞摄取,对A549细胞的活性有明显的抑制作用。

Objective The study aims at preparing the didodecyldimethylammonium bromide (DMAB)-modified PLGA nanoparticles (NPs) loading tetrandrine (Tet) (DMAB-Tet-PLGA-NPs) and investigating the preparation process, physicochemical characterization, in vitro cytotoxicity, and particle cellular uptake. Methods DMAB-Tet-PLGA-NPs were prepared by the emulsion solvent diffusion method and the preparation process was optimized with the uniform design experiment. The drug loading, entrapment efficiency (EE), and in vitro drug release were studied to evaluate the drug-loading property. The in vitro cytotoxicity against human lung cancer cell A549 was measured by the standard MTT assay. The particles cellular uptake in A549 was evaluated by qualitative and quantitative methods. Results DMAB-Tet-PLGA-NPs in the mean size of (205.40 ± 2.66) nm with spherical shape and showed positive surface charge. Drug loading and EE were (2.130 ± 0.035)% and (50.780 ± 3.253)%, respectively. DMAB-Tet-PLGA-NPs could retard drug release in pH 7.4 release media and the cumulative release was up to 64.56% over 48 h. And DMAB-Tet-PLGA-NPs showed the significant dose-and time-dependent cytotoxicity of Tet in vitro and well cellular uptake by A549. Conclusion DMAB-Tet-PLGA-NPs shows the good EE, uniform particle size, and could retard drug release in vitro. And DMAB-Tet-PLGA-NPs shows the significant cytotoxicity in vitro and well cellular uptake by A549.

国家自然科学基金面上项目(#81370980)