Laponite® gel formulation containing simvastatin for melanoma treatment

Melanoma is one of the most common recurrent malignancies in humans.A new Laponite® (LAP) gel containing the drug simvastatin (SIM), targeting topical treatment of melanoma, was developed, and evaluated using different techniques. First, a preformulation study was carried out, where the impact of LAP concentrations, gelation time and temperature on the gel`s apparent viscosity were evaluated. The effect of chemical enhancers of permeation, isopropyl myristate (MYR) and squalene (SQ), on the gel`s apparent viscosity was also assessed at this point. Based on the results obtained in preformulation, three optimized gels were proposed to incorporate the drug, named GS, GMS, and GSS. The gels were evaluated by SIM content, polarized light microscopy (PLM) and ex vivo permeation studies. The results obtained demonstrated a good drug loaded for all gels, GS (98.70 ± 0.69%), GMS (100.74 ± 5.68%), and GSS (97.46 ± 7.45%). The PLM showed the formation of tactoid structures for the samples containing the permeation enhancers MYR and SQ in the presence of SIM. The amount of drug permeated through the human skin (epidermis+dermis) after 24 h for each tested formulation was lower than 0.01% of total initial amount, suggesting a topical action of SIM. The stability studies performed for the final proposed formulation (GS) suggested a good stability for the evaluated parameters, SIM content, pH, apparent viscosity and for the count of viable microorganisms. The antibacterial and melanoma antitumoral activities for SIM were experimentally confirmed. LAP showed to be a good carrier for pharmaceutical formulations containing SIM, and it is a promising material for the development of products that aim to treat melanoma topically.