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一种靶向乳腺癌细胞的整合型茉莉酸甲酯透皮微乳系统的抗肿瘤疗效:体内外研究

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

作者信息

Yehia Rania, Hathout Rania M, Attia Dalia A, Elmazar Mohamed M, Mortada Nahed D

机构信息

Department of Pharmaceutics and Industrial Pharmacy, The British University in Egypt (BUE), Cairo, Egypt.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

出版信息

Colloids Surf B Biointerfaces. 2017 Jul 1;155:512-521. doi: 10.1016/j.colsurfb.2017.04.031. Epub 2017 Apr 23.

Abstract

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 0.07μlcmh. Cytotoxicity studies were carried out where the selected superlative formulation was further investigated on MCF-7 cell lines and scored an IC of 42.2μl/ml (equivalent to 8.3μl/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.

摘要

经皮靶向实体瘤是一种正在深入研究的新兴方法。在此背景下,微乳剂被报道为成功进行经皮给药最受青睐的载体之一。因此,本研究利用这些纳米载体来递送一种植物化学物质,即二氢茉莉酮酸甲酯(MDHJ),该物质先前已证明具有抗癌作用。据此,采用油、表面活性剂和助表面活性剂的几种组合并遵循水滴定法构建了伪三元相图。选择了两个体系,并利用实验设计(单纯形格子混合设计)通过小鼠皮肤的离体渗透研究来选择制剂进行进一步研究。测定的经皮通量达到了0.07μl/cm²/h的值。进行了细胞毒性研究,在MCF - 7细胞系上进一步研究了所选的最佳制剂,其IC₅₀为42.2μl/ml(相当于8.3μl/ml药物)。此外,使用艾氏实体癌进行了体内研究,并对肿瘤细胞进行了组织病理学检查,评估了与对照、安慰剂和纯药物相比制剂的肿瘤体积差异、肿瘤抑制百分比和坏死效应。所得结果表明,将所选制剂应用于荷瘤小鼠皮肤时具有显著的抗癌作用。

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