叶酸壳寡糖修饰的紫杉醇 PLGA纳米粒的体外释放及对 SK-OV-3增殖的抑制作用

摘要

Objective:To prepare PLGA nanoparticles modified with folic acid conjugated chitosan oligosaccharide containing pa-clitaxel (F-CS-PLGA-NPs) and study the inhibitory effect on SKOV-3. Methods:F-CS-PLGA-NPs were prepared by an interface dep-osition method, 30% ethanol was used as the release medium for the in vitro release profiles of nanoparticles, and MTT was adopted to evaluate the inhibitory effect of paclitaxel with different formulations and concentrations on SKOV-3. Results:The particle size and zeta potential of F-CS-PLGA-NPs was (321 ± 0. 76) nm and (22. 6 ± 0. 26) mV, respectively, the drug loading was (5. 1 ± 0. 25)%, and the encapsulation efficiency was (41. 96 ± 1. 96)%. F-CS-PLGA-NPs had a similar in vitro release profiles with the ordinary nanoparti-cles ( PLGA-NPs) . About 35% of paclitaxel was released from the nanoparticles in the initial 24 h, and then a near zero order release at a relative slow rate was shown, and the cumulative release rate in 144 h was about 75%. The results of cell experiments suggested that at the same paclitaxel concentration, the inhibition effect of F-CS-PLGA-NPs group was stronger than that of the PLGA-NPs group and the solution group. The inhibition effect of F-CS-PLGA-NPs could be reduced by free folic acid. Conclusion:PLGA nanoparticles modified with folic acid conjugated chitosan oligosaccharide can increase the targeting efficiency in SKOVS-3 tumor cells.%目的：：制备叶酸壳寡糖修饰的紫杉醇PLGA纳米粒(F-CS-PLGA-NPs),并考察其对人卵巢癌上皮细胞(SKOV-3)的抑制作用。方法：采用界面沉积法制备F-CS-PLGA-NPs,以30%乙醇作为释放介质考察修饰和未修饰纳米粒的体外释药情况, MTT法比较不同剂型和不同浓度紫杉醇对SKOV-3增殖的抑制作用。结果： F-CS-PLGA-NPs的粒径为(321±0.76) nm,电位为(22.6±0.26)mV,载药量为(5.1±0.25)%,包封率为(41.96±1.96)%。修饰和未修饰纳米粒的体外释药曲线相似,在最初24 h内约有35%药物释放,随后释药速度减慢,纳米粒以近零级方式释放,144 h累计释药率约为75%。细胞实验结果显示,在紫杉醇浓度相同的情况下,F-CS-PLGA-NPs在不同作用时间对细胞的抑制作用均强于紫杉醇溶液组和普通纳米粒组,F-CS-PLGA-NPs对SKOVS细胞增殖的抑制作用在一定程度上被游离叶酸减弱。结论：叶酸壳寡糖的修饰增加了纳米粒对SK-OVS-3细胞的靶向性。