Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr H S Gour University, Sagar, MP, India.
Biomaterials. 2012 Oct;33(29):7206-20. doi: 10.1016/j.biomaterials.2012.06.056. Epub 2012 Jul 17.
A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2 ± 2.5% in 24 h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3 ± 10.2 to 4.4 ± 1.3%) and control the release of PTX (43.6 ± 3.2% released in 24 h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using (99m)Tc-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24 h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel.
一种基于甘油单油酸酯 (GMO) 的紫杉醇 (PTX) 的聚乙二醇化药物递送系统通过优化各种参数来制备，以探索其在癌症治疗中的潜力。通过偏光显微镜、TEM、AFM 和 SAXS 对所制备的系统进行了表征，以揭示其液晶性质。由于基于 GMO 的 LCNPs 表现出高溶血毒性和更快释放包封药物（24 小时内释放 66.2 ± 2.5%），因此采用聚乙二醇化策略来提高血液相容性（溶血从 60.3 ± 10.2%降低至 4.4 ± 1.3%）并控制 PTX 的释放（24 小时内释放 43.6 ± 3.2%）。在 MCF-7 细胞系中评估了细胞毒性潜力和细胞摄取。此外，在荷 EAT（Ehrlich 腹水瘤）小鼠中进行了生物分布研究，使用 (99m)Tc（锝放射性核素）标记制剂，并观察到与普通制剂相比，PEG 化载体在 24 小时时具有更长的循环时间和更高的肿瘤积累（分别为 14 倍和 8 倍）。最后，进行了肿瘤生长抑制实验，15 天后，与初始肿瘤体积相比，对照组的肿瘤体积增加了 15 倍，而普通制剂和 PEG 化系统仅增加了 8 倍和 4 倍。结果表明，聚乙二醇化增强了基于 GMO 的系统的血液相容性和功效，可作为紫杉醇的有效静脉给药载体。
