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Int J Biol Macromol ; 165(Pt A): 1055-1065, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32987080

ABSTRACT

Due to the limited options for topical management of skin cancer, this study aimed at developing and evaluating nanoemulsions (NE) for topical delivery of the cytotoxic agent piplartine (piperlongumine). NEs were modified with chitosan or sodium alginate, and the effects on the physicochemical properties, piplartine delivery and formulation efficacy were evaluated. The nanoemulsion droplets displayed similar size (96-112 nm), but opposite charge; the polysaccharides improved piplartine penetration into and across the skin (1.3-1.9-fold) in a similar manner, increasing the ratio "drug in the skin/receptor phase" by 1.4-1.5-fold compared to the plain NE and highlighting their relevance for cutaneous localization. Oleic acid addition to the chitosan-containing NE further increased drug penetration (~1.9-2.0-fold), as did increases in drug content from 0.5 to 1%. The cytotoxicity of piplartine was ~2.8-fold higher when the drug was incorporated in the chitosan-containing NE compared to its solution (IC50 = 14.6 µM) against melanoma cells. The effects of this nanocarrier on 3D melanoma tissues were concentration-related; at 1%, piplartine elicited marked epidermis destruction. These results support the potential applicability of the chitosan-modified nanoemulsion containing piplartine as a new strategy for local management of skin cancer.


Subject(s)
Emulsions/chemistry , Melanoma/drug therapy , Nanoparticles/chemistry , Skin Neoplasms/drug therapy , Alginates/chemistry , Cell Proliferation/drug effects , Chitosan/chemistry , Cytotoxins/chemistry , Emulsions/pharmacology , Humans , Melanocytes/drug effects , Melanocytes/pathology , Piperidones/chemistry , Piperidones/pharmacology , Skin Neoplasms/pathology
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