LAUSR

Abstract Background The wide spectrum of antitumoral mechanisms of imiquimod (IMQ), made it a good candidate for topical therapy of melanoma. However, physicochemical properties make IMQ formulation a difficult task. Solubility and skin penetration of IMQ are increased when loaded into ultradeformable nanovesicles. Objective Survey the in vitro anti-melanoma activity of IMQ loaded into two types of ultradeformable nanovesicles: archaeosomes (UDA-IMQ) (containing sn-2,3 ether-linked phytanyl saturated archaeolipids extracted from Halorubrum tebenquichense) and liposomes lacking archaeolipids (UDL-IMQ). Methods We prepared and structurally characterized UDA-IMQ and UDL-IMQ. Cytotoxicity was determined on human melanoma cells (SK-Mel-28) and keratinocytes (HaCaT cells) by MTT assay and LDH release. The cellular uptake was determined by flow cytometry. Apoptosis/necrosis induction was determined by fluorescence microscopy after double staining with YO-PRO-1® and propidium iodide. Results Neither IMQ nor IMQ-nanovesicles reduced the viability of HaCaT cells; but UDL-IMQ (371 nm, −24 mV ζ potential, 31 µg IMQ/mg lipids) and UDA-IMQ (216 nm, −32 mV ζ potential, 61 µg IMQ/mg lipids) showed time and concentration-dependent cytotoxicity on SK-Mel-28 that resulted between 4 and 33 folds higher than free IMQ, respectively. While both UDA-IMQ and UDL-IMQ retained 60% of IMQ against dilution, UDA-IMQ uptaken by SK-Mel-28 cells was nine-fold higher than UDL-IMQ. UDL-IMQ induced early apoptosis, but UDA-IMQ induced both apoptosis and necrosis on SK-Mel-28 cells. Conclusions UDA-IMQ was innocuous to keratinocytes but was highly uptaken and induced apoptosis and necrosis on melanoma cells, being a candidate for future investigations as adjuvant topical anti-melanoma therapy.