Cordeiro Arthur Poester, Feuser Paulo Emílio, Figueiredo Pedro Graupen, Cunha Elizabeth Sousa da, Martinez Glaucia Regina, Machado-de-Ávila Ricardo Andrez, Rocha Maria Eliane Merlin, Araújo Pedro Henrique Hermes de, Sayer Claudia
Department of Chemical and Food Engineering, Federal University of Santa Catarina, SC, Brazil.
Department o Biochemistry and Molecular Biology of Federal University of Paraná, Brazil.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111651. doi: 10.1016/j.msec.2020.111651. Epub 2020 Oct 21.
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 IC 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.
使用纳米颗粒作为药物递送系统来同时携带多种治疗剂，是创造新的协同治疗方法以及开发下一代癌症疗法的一个有吸引力的想法。因此，本研究的目标是将亲水性药物二乙基二硫代氨基甲酸钠（DETC）和疏水性药物4-硝基查耳酮（4NC）同时包封在蜂蜡纳米颗粒（BNs）中，以评估该组合对黑色素瘤（B16F10）细胞的体外协同活性。BNs是在无有机溶剂的情况下通过水/油/水双重乳液法制备的。透射电子显微镜成像和动态光散射分析表明形成了半球形的BNs，平均直径低于250nm，分布相对较窄，且zeta电位为负。双重乳液技术被证明对于同时包封DETC和4NC是有效的，包封效率分别为86.2%和98.7%，并且这种包封不影响BNs的物理化学性质。负载在BNs中的DETC和4NC对B16F10细胞表现出比游离4NC和DETC更高的细胞毒性。这种同时包封导致DETC和4NC对B16F10细胞产生协同作用，使细胞活力从46%（DETC BNs）和54%（4NC BNs）降至64%（DETC+4NC BNs）。因此，DETC+4NC的半数抑制浓度（IC）也低于单独包封时以及游离DETC或4NC的IC。因此，DETC和4NC能够有效地同时包封在BNs中，并且这种药物组合能够对B16F10细胞产生体外协同治疗效果。
