Anti-tumor efficacy of an integrated methyl dihydrojasmonate transdermal microemulsion system targeting breast cancer cells: In vitro and in vivo studies

摘要

Targeting solid tumors transdermally is an emerging approach that is currently under intense investigation. In this context, microemulsions are reported as one of the most favored carriers for successful transdermal drug delivery. Thereby, these nano-carriers were utilized in this study for the delivery of a phytochemical, namely methyl dihydrojasmonate (MDHJ), which has previously demonstrated an anticancer effect. Accordingly, pseudoternary phase diagrams were constructed using several combinations of oils, surfactants and co-surfactants and following the water titration method. Two systems were selected and an experimental design (Simplex Lattice Mixture Design) was utilized to select formulations for further investigation through an ex vivo permeation study through mouse skin. Transdermal fluxes were determined reaching a value of 0.07 mu l cm(-2) h(-1). Cytotoxicity studies were carried out where the selected superlative formulation was further investigated on MCF-7 cell lines and scored an IC50 of 42.2 mu l/ml (equivalent to 8.3 mu l/ml drug). Further, in vivo investigations were performed using Ehlirch solid carcinoma and histopathological examination of the tumor cells evaluating the tumor volume differences, tumor inhibition percentages and the necrotic effect of the formulation compared to control, placebo and pure drug. The obtained results showed significant anticancer effects of the selected formulation when applied on the tumor bearing mice skin. (C) 2017 Elsevier B.V. All rights reserved.