目的:研究的目的是评估由D-α-生育酚基聚乙二醇琥珀酸酯(TPGS)和1,2-二硬脂酰-甘油-3-磷酸乙醇胺-N-制备的混合胶束的适用性。甲氧基(聚乙二醇)-2000](DSPE-PEG)封装难溶性抗癌药物芬瑞宁(4-HPR)。
方法:用平衡法测定表面活性剂的增溶能力后,使用溶剂流延技术从不同的4-HPR:TPGS:DSPE-PEGw/w比率开始制备胶束。研究所得制剂在储存条件下和稀释时的稳定性,模拟静脉给药后生理浓度的达到。胶束的表征包括DL%的测定,EE%,粒度分布,Z电位,和DSC热分析。通过MTT论文对HTLA-230和SK-N-BE-2C神经母细胞瘤细胞进行了细胞毒性研究。
结果:胶体分散体的平均直径为12nm,负Zeta电位,和狭窄的尺寸分布。将4-HPR配制在混合胶束中,包封率为88%,表观溶解度增加了363倍。4-HPR截留保持稳定,直到表面活性剂浓度为2.97E-05M。负载的胶束表现出缓慢释放行为,约28%的药物在24小时后释放。在最具抗性的SK-N-BE-2C细胞上,在降低细胞活力方面,包封的4-HPR比游离的4-HPR显著更活跃。
结论:负载胶束证明了它们作为一种新的辅助工具的适用性,可能用于治疗神经母细胞瘤。
OBJECTIVE: The purpose of the study was to evaluate the suitability of mixed micelles prepared with D-α-tocopheryl polyethylene glycol succinate (TPGS) and 1,2- distearoyl-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) to encapsulate the poorly soluble anticancer drug fenretinide (4-HPR).
METHODS: After assaying the solubilization ability of the surfactants by the equilibrium method, the micelles were prepared using the solvent casting technique starting from different 4-HPR:TPGS: DSPE-PEG w/w ratios. The resulting formulations were investigated for their stability under storage conditions and upon dilution, modelling the reaching of physiological concentrations after intravenous administration. The characterization of micelles included the determination of DL%, EE %, particle size distribution, Z-potential, and thermal analysis by DSC. The cytotoxicity studies were performed on HTLA-230 and SK-N-BE-2C neuroblastoma cells by the MTT essay.
RESULTS: The colloidal dispersions showed a mean diameter of 12 nm, negative Zeta potential, and a narrow dimensional distribution. 4-HPR was formulated in the mixed micelles with an encapsulation efficiency of 88% and with an increment of the apparent solubility of 363-fold. The 4-HPR entrapment remained stable up to the surfactants\' concentration of 2.97E-05 M. The loaded micelles exhibited a slow-release behaviour, with about 28% of the drug released after 24 h. On the most resistant SK-N-BE-2C cells, the encapsulated 4-HPR was significantly more active than free 4-HPR in reducing cell viability.
CONCLUSIONS: Loaded micelles demonstrated their suitability as a new adjuvant tool potentially useful for the treatment of neuroblastoma.