负载小檗碱单壁碳纳米管递药系统的制备及体外评价

Preparation and in vitro evaluation of a berberine-loaded single-walled carbon nanotubes drug delivery system

目的:制备负载小檗碱单壁碳纳米管递药系统(F127/SWCNTs-COOH/Ber),并考察其对前列腺肿瘤的抑制作用。方法:采用超声法制备将小檗碱(berberine,Ber)负载于功能化羧基单壁碳纳米管(F127/SWCNTs-COOH)上,以包封率和载药量为指标,通过单因素试验考察优化处方制备工艺。对F127/SWCNTs-COOH/Ber的粒径及Zeta电位、体外溶出度及吸附特性等进行考察;采用人前列腺癌PC-3细胞进行体外细胞毒性评价。结果:最佳处方制备工艺,药物与载体投料比为1∶1,探超功率为200 W,探超次数为30次。制备的F127/SWCNTs-COOH/Ber平均粒径与电位分别为(182.3±11.64)nm、(–3.44±0.17)mV;包封率与载药量分别为81.09%、38.86%;30 min内在人工肠液和人工胃液中累积溶出率分别为94.02%、76.69%。F127/SWCNTs-COOH对小檗碱的吸附符合准二级吸附动力学模型。MTT实验与细胞摄取实验结果表明,F127/SWCNTs-COOH/Ber对PC-3细胞的增殖抑制作用显著高于单独使用小檗碱,可以更有效地将负载的小檗碱递送进入肿瘤细胞发挥治疗作用。结论:F127/SWCNTs-COOH/Ber递药系统制备成功,可提高小檗碱对前列腺肿瘤PC-3细胞的增殖抑制作用及细胞摄取效率,为前列腺癌治疗提供了一种潜在的递送载体。

OBJECTIVE To prepare a drug delivery system of a single-walled carbon nanotubes loaded berberine(F127/SWCNTs-COOH/Ber)and explore the inhibitory effect on prostate cancer.METHODS Berberine was loaded onto F127/SWCNTs-COOH by ultrasonic method and formulation process was optimized by single-factor test using encapsulation efficiency and drug loading as parameters.Particle size,Zeta potential,in vitro dissolution and adsorption characteristics of F127/SWCNTs-COOH/Ber were explored.And cytotoxicity was evaluated in PC-3 cells.RESULTS The optimal formulation process for F127/SWCNTs-COOH/Ber was as follows:ratio of carrier to drug was 1∶1,ultrasonic power 200 W and ultrasonic frequency 30 times.Average particle size and Zeta potential were(182.3±11.64)nm and(–3.44±0.17)mV;encapsulation efficiency and drug loading 81.09%and 38.86%;cumulative dissolution rates within 30 min in simulated intestinal fluid and simulated gastric fluid 94.02%and 76.69%.The absorption of berberine in F127/SWCNTs-COOH followed the pseudo-secondorder model.Anti-cancer activity of F127/SWCNTs-COOH/Ber was significantly higher than that of berberine alone,thereby enabling a more effective delivery of loaded berberine into tumor cells for therapeutic purposes.CONCLUSION F127/SWCNTs-COOH/Ber has successfully prepared,demonstrating its potential of enhancing the inhibitory effect on the proliferation of PC-3 cells in PC and cell uptake efficiency.This provides a promising delivery vector for treating prostate cancer.