4.3 Article

In vitro synergic activity of diethyldithiocarbamate and 4-nitrochalcone loaded in beeswax nanoparticles against melanoma (B16F10) cells

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ELSEVIER
DOI: 10.1016/j.msec.2020.111651

关键词

Solid lipid nanoparticles; Simultaneous encapsulation; Synergic effect; Skin cancer; Double emulsion

资金

  1. CAPES - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [88887.310560/2018-00]
  2. CNPq -Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [310107/2015-6]
  3. INCT Redoxoma, FINEP (CT-Infra)

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The study aimed to encapsulate sodium diethyldithiocarbamate (DETC) and 4-nitrochalcone (4NC) in beeswax nanoparticles (BNs) to evaluate the synergistic activity against melanoma cells. The results showed that DETC and 4NC loaded in BNs exhibited higher cytotoxicity towards B16F10 cells and the simultaneous encapsulation led to a synergistic effect on cell viability.
The use of nanoparticles as drug delivery systems to simultaneously carry several therapeutic agents is an attractive idea to create new synergic treatments and to develop the next generation of cancer therapies. Therefore, the goal of this study was the simultaneous encapsulation of a hydrophilic drug, sodium diethyldithiocarbamate (DETC), and a hydrophobic drug, 4-nitrochalcone (4NC), in beeswax nanoparticles (BNs) to evaluate the in vitro synergic activity of this combination against melanoma (B16F10) cells. BNs were prepared by water/oil/water double emulsion in the absence of organic solvents. Transmission electron microscopy imaging and dynamic light scattering analyses indicated the formation of BNs with a semispherical shape, average diameter below 250 nm, relatively narrow distributions, and negative zeta potential. The double emulsion technique proved to be effective for the simultaneous encapsulation of DETC and 4NC with efficiencies of 86.2% and 98.7%, respectively, and this encapsulation did not affect the physicochemical properties of the BNs. DETC and 4NC loaded in BNs exhibited a higher cytotoxicity toward B16F10 cells than free 4NC and DETC. This simultaneous encapsulation led to a synergic effect of DETC and 4NC on B16F10 cells, decreasing the cell viability from 46% (DETC BNs) and 54% (4NC BNs) to 64% (DETC+4NC BNs). Therefore, the IC50 of DETC+4NC was also lower than that of either when individually encapsulated, and that of free DETC or 4NC. Therefore, DETC and 4NC were efficiently simultaneously encapsulated in BNs and this drug combination was able to generate an in vitro synergic therapeutic effect on B16F10 cells.

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