The topical delivery route is proposed as an alternative or adjunctive approach to melanoma treatment, since the target site for melanoma treatment—the epidermal basal layer—is potentially accessible by this route. Microemulsion systems are effective delivery vehicles for enhanced, targeted skin delivery. This work investigated the effect of Rose Bengal (RB) and RB-loaded self-emulsifying microemulsions (SEMEs) on growth inhibition of human melanoma and normal skin cell monolayers, the safety of the excipients incorporated in SEMEs on human cell lines, and the in-vitro human skin penetration of RB delivered in SEMEs and control solution. Cellular toxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the growth inhibitory mechanism of RB was investigated by flow cytometry using PI staining. Unloaded SEMEs caused reduced cellular toxicity compared to the surfactant excipient, Labrasol^®. RB-loaded SEMEs increased cell growth inhibition compared to the RB aqueous solution. Flow cytometry revealed apoptotic cells after treatment with RB-loaded SEMEs, indicating that apoptosis may be one of the mechanisms of cell death. Preliminary results of multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) analysis showed deeper penetration with greater skin concentrations of RB delivered from SEMEs compared to the RB aqueous solution. This study highlights the enhanced skin penetration and antimelanoma effects of RB loaded in a SEME system.

中文翻译：

---

用于玫瑰孟加拉皮肤递送的水包油型自乳化微乳液的开发：抗黑素瘤特性的研究

提议将局部递送途径作为黑素瘤治疗的替代或辅助方法，因为黑素瘤治疗的目标部位（表皮基底层）可通过该途径进入。微乳液系统是有效的输送工具，可增强目标皮肤的输送能力。这项工作研究了玫瑰孟加拉（RB）和负载RB的自乳化微乳液（SEME）对人黑素瘤和正常皮肤细胞单层细胞生长抑制的作用，SEME中掺入的赋形剂对人细胞系的安全性以及SEME和对照溶液中递送的RB对人体皮肤的体外渗透。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物（MTT）分析评估细胞毒性，并使用PI染色通过流式细胞术研究RB的生长抑制机制。^®。与RB水溶液相比，负载RB的SEMEs增加了细胞生长抑制作用。流式细胞仪揭示了用RB加载的SEME处理后的凋亡细胞，这表明凋亡可能是细胞死亡的机制之一。带有荧光寿命成像（MPM-FLIM）分析的多光子显微镜的初步结果显示，与RB水溶液相比，从SEME递送的皮肤浓度更高的RB具有更深的穿透力。这项研究突出了SEME系统中负载的RB增强的皮肤渗透和抗炭疽的作用。