Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models

Skin Cancer

Int J Biol Macromol. 2020 Sep 25:S0141-8130(20)34527-X. doi: 10.1016/j.ijbiomac.2020.09.167. Online ahead of print.


Due to the limited options for topical management of skin cancer, this study aimed at developing and evaluating nanoemulsions (NE) for cutaneous 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.