Department of Nanotechnology and Nanomedicine, Institute for Graduate Studies in Science Engineering, Hacettepe University, Ankara, Turkey.
Bioengineering Division, Institute for Graduate Studies in Science & Engineering, Hacettepe University, Ankara, Turkey.
Pharm Dev Technol. 2020 Dec;25(10):1192-1203. doi: 10.1080/10837450.2020.1803910. Epub 2020 Aug 4.
Malignant melanoma is a type of skin cancer with high risk of metastasis. 5-Fluorouracil is commonly used for treatment of skin cancer, however its penetration through the skin is found to be insufficient in some cases. Therefore, we optimized its pharmacokinetics by fabricating 5- Fluorouracil-loaded nanoliposome formulations modified with Poly-L-lysine coating. 5-Fluorouracil-loaded nanoliposome formulations were prepared using dipalmitoylphosphatidylcholine, dicethylphosphate and cholesterol having encapsulation efficiency of 45±9.61%. The particle size, zeta potential, polydispersity index and encapsulation rate of the prepared formulation was found to be 237.9±0.986nm, 41.4±1.060mV, 0.233±0.019 and 88.2±7.85%, respectively. Surface characterization, molecular structure and thermal property illumination of the formulations were performed alongside stability studies. The release of 5-FU from Lipo-FU6 and PLL-1 formulations was investigated by dialysis membrane method. Within the first 12hours, the percentage release of 5-FU from Lipo-FU6 and PLL-1 formulations was observed to be 47.17% and 20.84%, respectively. Moreover, the cytotoxicity study on A431 epidermal carcinoma cell lines has revealed that 5-FU-loaded formulations were toxic to cells unlike the 5-FU free formulations. In conclusion, PLL coated nanoliposome formulations showed a potential to be an effective option for further combined drug/gene therapy applications.
恶性黑色素瘤是一种具有高转移风险的皮肤癌。5-氟尿嘧啶常用于治疗皮肤癌，但在某些情况下，发现其穿透皮肤的能力不足。因此，我们通过制备聚-L-赖氨酸修饰的载 5-氟尿嘧啶纳米脂质体制剂来优化其药代动力学。使用二棕榈酰磷脂酰胆碱、二乙基磷酸酯和胆固醇制备载 5-氟尿嘧啶纳米脂质体制剂，包封效率为 45±9.61%。所制备制剂的粒径、Zeta 电位、多分散指数和包封率分别为 237.9±0.986nm、41.4±1.060mV、0.233±0.019 和 88.2±7.85%。对制剂进行了表面特性、分子结构和热性能的表征以及稳定性研究。通过透析膜法研究了 Lipo-FU6 和 PLL-1 制剂中 5-FU 的释放。在前 12 小时内，Lipo-FU6 和 PLL-1 制剂中 5-FU 的释放百分比分别为 47.17%和 20.84%。此外，对 A431 表皮癌细胞系的细胞毒性研究表明，载 5-FU 制剂对细胞有毒性，而游离 5-FU 制剂则没有。总之，PLL 涂层纳米脂质体制剂有潜力成为进一步联合药物/基因治疗应用的有效选择。
