Affiliation:
1. School of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300350 P. R. China
2. Skin Barrier Research Group Faculty of Pharmacy Charles University Akademika Heyrovského 1203 Hradec Králové 50005 Czech Republic
3. Department of Chemistry State University of New York at Buffalo Buffalo NY 14260 USA
4. Department of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USA
Abstract
AbstractTopical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad‐spectrum second‐generation taxane cytotoxic agent, can be dissolved in α‐tocopherol at high concentrations exceeding 100 mg mL−1. 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α‐tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm−2 within 24 h), while no detectable drug permeates when CTX is dissolved in α‐tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α‐tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL−1), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL−1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α‐tocopherol solvent warrants further study as a treatment for skin malignancies.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Grantová Agentura České Republiky
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)