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Cisplatin (Cis) is an effective cytotoxic agent, but its administration has been challenged by kidney problems, reduced immunity system, chronic neurotoxicity, and hemorrhage. To address these issues, pH-responsive non-ionic surfactant vesicles (niosomes) by Span 60 and Tween 60 derivatized by cholesteryl hemisuccinate (CHEMS), a pH-responsive agent, and Ergosterol (helper lipid), were developed for the first time to deliver Cis. The drug was encapsulated in the niosomes with a high encapsulation efficiency of 89%. This system provided a responsive release of Cis in pH 5.4 and 7.4, thereby improving its targeted anticancer drug delivery. The noisome bilayer model was studied by molecular dynamic simulation containing Tween 60, Span 60, Ergosterol, and Cis molecules to understand the interactions between the loaded drug and noisome constituents. We found that the platinum and chlorine atoms in Cis are critical factors in distributing the drug between water and bilayer surface. Finally, the lethal effect of niosomal Cis was investigated on the MCF7 breast cancer cell line using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results from morphology monitoring and cytotoxic assessments suggested a better cell-killing effect for niosomal Cis than standard Cis. Together, the synthesis of stimuli-responsive niosomes could represent a promising delivery strategy for anticancer drugs.

pH-responsive cisplatin-loaded niosomes: synthesis, characterization, cytotoxicity study and interaction analyses by simulation methodology