Evaluation of the potential of cationic solid lipid nanoparticles for incorporation of curcumin in the topical treatment of melanoma

Abstract

Epidemiological data indicate cancers as the third leading cause of death in the world, being skin cancer the most prevalent of them. Melanoma (MEL) is less common of the cutaneous tumors, but with highest mortality, since its can progress to aggressive tumors, that suffer metastatic and are resistant to therapy. The choice of treatment involves the administration of chemotherapy, which may have cytotoxic also on healthy cells, decreasing significantly the quality and survival of patients. Therefore, many researchers are working diligently on finding substances including those from natural sources, which has therapeutic interest. Curcumin (CUM), naturally compound isolated from the rhizomes of Curcuma longa, has shown activity in the treatment of MEL, decreasing the levels of cyclin D1, increasing the activity of tumor suppressor proteins of RB family and inhibiting production of reactive oxygen species (ROS) and cytokine important in tumor growth, such as tumor necrosis factor and interleukin-1. However, its clinical use is facing many challenges, mainly related to the low oral bioavailability. Thus, its topical administration may be convenient to locate it on their site of action. However, some of their physicochemical properties, such as limited aqueous solubility, hampers its effectiveness therapeutic topical since it has low skin penetration. Technological strategies, such as cationic solid lipid nanoparticles (SLN), which have the ability to compartmentalize, efficiently, several groups of active and modify their properties and behavior in a biological environment, are promising for topical administration of CUM, especially in virtue of their interaction with the stratum corneum and other layers of the skin, due to the small particle size and the capacity of arrangement of drug with a protective effect and sustainer of release. In addition, the positive charge of these systems may facilitate targeting to cancer cells that have high density of negative charges, because exposure of phosphatidylserine (PS) on the surface of cell membranes. This project intend to develop, characterize and evaluate the in vitro biological effects of cationic SLN for incorporating of CUM to optimize the use of this substance in the topical treatment of MEL.