Development of an Oil-in-Water Self-Emulsifying Microemulsion for Cutaneous Delivery of Rose Bengal: Investigation of Anti-Melanoma Properties

Abstract

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.

Novel Gel Microemulsion as Topical Drug Delivery System for Curcumin in Dermatocosmetics

“…Because the number of parameters was not identical for each model, and R 2 increases with increasing numbers of parameters, for the selection of the mathematical model which fits best on the experimental data, it was necessary to use the adjusted correlation coefficient (R 2 adj ) [ 56 , 57 ]. This formula was used: R 2 adjusted = 1 − (( n − 1) × (1 − R2))/( n p − 1), where “p” is the number of parameters in the model and “ n ” is the number of experimental data points [ 58 ].…”

Triazine–Carbosilane Dendrimersomes Enhance Cellular Uptake and Phototoxic Activity of Rose Bengal in Basal Cell Skin Carcinoma Cells

“… 63–66 In the case of RB, increased cellular uptake seems to be critical for phototoxic activity: regardless of the level of singlet oxygen generation, RB-loaded dendrimersomes generate significantly higher levels of intracellular ROS, which translates into a stronger phototoxic effect. The IC 50 values for RB-loaded dendrimersomes in vitro are remarkably low (~1 µM RB for both formulations), considerably lower than those for most formulations mentioned above (for instance 28 , 30 , 32 , 36 ). Importantly, the dark toxicity of RB-loaded dendrimersomes is negligible in the concentration range used.…”

Ultraviolet Radiation Protective and Anti-Inflammatory Effects of Kaempferia galanga L. Rhizome Oil and Microemulsion: Formulation, Characterization, and Hydrogel Preparation

“…The IC 50 values of K. galanga rhizome oil and microemulsion were 6.8 mg/mL and 0.6 mg/mL, respectively. A previous study reported IC 50 values of 100.60 μg/mL, 83.04 μg/mL, and 94.75 μg/mL for ethyl-cinnamate, ethyl-p-methoxy-cinnamate, and trans-cinnamaldehyde, respectively [ 37 ] These results suggested that the microemulsion enhanced the cytotoxicity of K. galanga rhizome oil to RAW 264.7 cells, which was probably due to the enhancing solubility and penetration of the oil through the cell membrane via the surfactant of the microemulsion [ 38 , 39 , 40 ]. The cytotoxicity criteria of K. galanga rhizome oil, microemulsion containing oil, and blank microemulsion against RAW 264.7 cells conformed with ISO 10993–5:2009, which describes that reduction of cell viability by more than 30% is considered a cytotoxic effect.…”