Department of Pharmaceutics Faculty of Pharmacy, Deraya University, Minia, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
J Pharm Pharmacol. 2022 Jul 15;74(7):1027-1039. doi: 10.1093/jpp/rgac013.
Metformin-loaded liposomes were optimized for enhanced antiproliferative activity against melanoma.
Box-Behnken design and response surface methodology were employed to optimize entrapment efficiency, ex-vivo permeation and vesicle size. The optimized formulation was prepared by both the lipid hydration method and the modified injection method for comparison. Different concentrations of Pluronic F127 were employed for modification. Selected Pluronic-modified formulation (lipid molar concentration 55 mmol, cholesterol 30% and drug loading 52.9 mg) was characterized for morphology, entrapment efficiency, permeation and vesicle size.
The optimized formulation resulted in entrapment efficiency of 41.7 ± 0.01%, vesicle size of 1.405 ± 0.061 µm and percentage of permeation was 67 ± 5.5%. The improved cytotoxic effect of the selected formulation against melanoma mice B16 cell line compared with metformin solution was determined using MTT assay. Compared with the corresponding drug solution, the Pluronic-modified optimized liposomes displayed a highly efficient cytotoxic effect as evidenced by significant lowering in IC50 -887.3 ± 23.2 and 26.71 ± 0.69 μg/ml, respectively, P < 0.0001.
This study introduces an optimized liposomal formulation with enhanced cytotoxic effect against melanoma B16 cell line.
优化载有二甲双胍的脂质体，以增强其对黑色素瘤的抗增殖活性。
采用 Box-Behnken 设计和响应面法优化包封率、体外渗透和囊泡大小。采用脂质水化法和改良注射法制备优化配方，并进行比较。采用不同浓度的 Pluronic F127 进行修饰。选择 Pluronic 修饰的配方（脂质摩尔浓度 55mmol，胆固醇 30%，药物载量 52.9mg）进行形态、包封率、渗透和囊泡大小的特征描述。
优化后的配方得到的包封率为 41.7±0.01%，囊泡大小为 1.405±0.061μm，渗透百分比为 67±5.5%。通过 MTT 测定，确定了选定配方对黑色素瘤 B16 细胞系的细胞毒性作用优于二甲双胍溶液。与相应的药物溶液相比，Pluronic 修饰的优化脂质体显示出高效的细胞毒性作用，IC50 分别显著降低了 887.3±23.2 和 26.71±0.69μg/ml，P<0.0001。
本研究介绍了一种针对黑色素瘤 B16 细胞系的具有增强细胞毒性作用的优化脂质体配方。
