Preparation of Rhein-loaded hyaluolimosomes as a topical nanocarrier for melanoma: physicochemical characterization, ex-vivo permeation and human melanoma cell line studies, A375

Rhein (RH) is a promising phytochemical with well-documented pharmacological effects in several types of cancer. However, its pharmacological activity in skin cancer has not been studied. Moreover, RH suffers from numerous limitations that handicap its clinical applications, such as its poor aqueous solubility and dermal bioavailability. Herein, this study highlights, for the first time, RH application on skin cancer human melanoma cell line A375 and determines its IC50, the development of a novel rhein-loaded transferosomes; hyaluolimosomes, and its evaluation as a free drug and nano-drug. The formation of the RH-PL complex (RH-PLC) was verified by infrared spectroscopy, thermal analysis <i>via</i> differential scanning calorimetry, and structural examination through X-ray powder diffraction. Studies on in-vitro release and ex-vivo permeation and skin deposition showed the superiority of hyaluolimosomes to significantly improve RH release, skin permeation, and deposition compared with the free drug. Cell viability studies on A375 revealed a significant reduction in IC50 of hyaluolimosomes at 31.3 µg/mL compared to 434.8 µg/mL of rhein (12.89 fold) with safety profiles. The present study successfully achieved its primary objective by demonstrating cytotoxic activity against the melanoma cell line. On the other hand, an important issue of concurrent cytotoxicity was observed on HDFa cells, highlighting the need for incorporating active targeting strategies in future preclinical investigations.