Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
Int J Pharm. 2020 Sep 25;587:119626. doi: 10.1016/j.ijpharm.2020.119626. Epub 2020 Jul 10.
Local application of anticancer drugs provides a potential mode of chemotherapy for cutaneous melanoma with high compliance. However, the efficiency of drug delivery is highly limited by the physiological barrier from the skin to the tumor, which can not achieve the desired therapeutic effect. In the study, we designed ibuprofen-modified methoxy poly (ethylene glycol)-poly (ethylene imine) polymer to prepare paclitaxel-loaded micelles (PTX-M) and Carbopol 940 hydrogel containing PTX-M (PTX-Gel) to improve skin paclitaxel delivery for the local melanoma treatment. The PTX-M performed well both in the skin penetration and retention study. FT-IR analysis showed that PTX-M or PTX-Gel mainly changed the spatial structure of skin lipid and keratin, thus increasing the fluidity of lipid molecules in the stratum corneum, and the polymer was positively charged to enhance the skin permeation and deposition. Moreover, the positive charge also promoted the cellular uptake of PTX-M in B16 melanoma, resulting in better in vitro cytotoxicity of PTX-M to B16 cells Taxol®. As for in vivo against B16 cells solid tumor test, the Taxol® plus PTX-M/Gel group showed preferable anticancer activity than Taxol® alone.
局部应用抗癌药物为皮肤黑色素瘤提供了一种潜在的化疗模式，具有很高的顺应性。然而，药物输送的效率受到皮肤到肿瘤的生理屏障的高度限制，无法达到理想的治疗效果。在这项研究中，我们设计了布洛芬修饰的甲氧基聚乙二醇-聚亚乙基亚胺聚合物，以制备紫杉醇负载的胶束（PTX-M）和含有 PTX-M 的卡波姆 940 水凝胶（PTX-Gel），以改善皮肤紫杉醇的递送，用于局部黑色素瘤的治疗。PTX-M 在皮肤渗透和保留研究中表现良好。FT-IR 分析表明，PTX-M 或 PTX-Gel 主要改变了皮肤脂质和角蛋白的空间结构，从而增加了角质层中脂质分子的流动性，聚合物带正电荷，增强了皮肤的渗透和沉积。此外，正电荷还促进了 PTX-M 在 B16 黑色素瘤中的细胞摄取，从而使 PTX-M 对 B16 细胞的体外细胞毒性优于紫杉醇®。至于体内针对 B16 细胞实体瘤的测试，紫杉醇®加 PTX-M/Gel 组显示出比紫杉醇®单独使用更好的抗癌活性。
