Paclitaxel skin delivery by micelles-embedded Carbopol 940 hydrogel for local therapy of melanoma

• Published in: International journal of pharmaceutics 2020-09, Vol.587, p.119626-119626, Article 119626
• Main Authors: Xu, Hongmei, Wen, Yi, Chen, Shiyu, Zhu, Li, Feng, Runliang, Song, Zhimei
• Format: Article
• Language: English
• Subjects: Carbopol 940; Melanoma; Micelles; Paclitaxel; Skin drug delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119626

[Display omitted] •Paclitaxel-loaded ibuprofen-modified MPEG-PEI micelles (PTX-M) were prepared.•The micelles improved skin deposition and cellular uptake of paclitaxel, causing higher cytotoxicity against melanoma than Taxol.•The combination of Taxol and PTX-M-embedded hydrogel showed higher in vivo activity against melanoma than Taxol alone. 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.