PH-responsive oleic acid based nanocarriers: Melanoma treatment strategies

Abstract

Numerous clinical observations indicate that, despite novel therapeutic approaches, a high percentage of melanoma patients is non-responder or suffers of severe drug-related toxicity. To overcome these problems, we considered the option of designing, preparing and characterizing nanoemulsions and niosomes containing oleic acid, a pH-sensitive monounsaturated fatty acid holding per se an antimetastatic and anti-inflammatory role in melanoma. These new nanostructures will allow in vivo administration of oleic acid, otherwise toxic in its free form. For pulmonary route chitosan, a mucoadhesive agent, was enclosed in these nanocarriers to improve residence time at the lung site. A deep physical and chemical characterization was carried out evaluating size, ζ -potential, microviscosity, polarity as well as stability over time and in culture media. Moreover, their pH-sensitivity was evaluated by fluorometric assay. Cytotoxicity and cellular uptake were assessed in cultured normal fibroblasts and human melanoma cell lines. Interestingly, results obtained confirm nanocarrier stability and pH-sensitivity, associated to absence of cell toxicity, efficient cellular uptake and retention. Therefore, these new pH-sensitive oleic acid-based nanostructures could represent, by combining drug delivery in a pH-dependent manner with the antimetastatic potential of this fatty acid, a powerful strategy for more specific medicine against metastatic melanoma.