Enhancement of cytotoxicity of diallyl disulfide toward colon cancer by Eudragit S100/PLGA nanoparticles

According to WHO cancer is the second leading cause of death globally, amounting to about 1 in 6 deaths. Among these, colon cancer is the third leading cause of mortalities worldwide. Current measures for cancer treatment: chemotherapy, radiation, and surgery are accompanied by myriad side effects. In light of a mediocre success of synthetic drugs against cancer exploring the treasure of naturally occurring compounds with anti-cancer activity can be an effective strategy.

Diallyl disulfide (DADS), a dietary phytochemical derived from garlic possesses a substantial anti-cancer activity against colon cancer. Nevertheless, its poor water solubility and restricted selectivity towards tumor tissues have limited its clinical applications. Moreover, to deliver intact drugs is another major concern in the treatment of ailments associated with the colon. To address these aforementioned clinically significant issues, we report dual functioning DADS loaded polymeric nanoparticles composed of a combination of Eudragit S100 (ES100) as a pH-sensitive polymer for targeted delivery to colon and poly (lactic-co-glycolic acid) (PLGA) as a biodegradable polymer for sustained release of DADS along with their physicochemical characteristics. Secondly, we report in-vitro cytotoxicity study, cell cycle analysis, and cellular uptake study of DADS loaded polymeric nanoparticles (ES100/PLGA-NPs) in CT26 murine colon carcinoma cells.

ES100/PLGA-NPs elucidated higher cell growth inhibition and low IC₅₀ value, in comparison to free DADS. Cellular uptake study exhibited the internalization of ES100/PLGA-NPs. These outstanding data illuminate that the fabricated polymeric nanoparticles as an effective modality for site-specific targeting and its use to augment the efficacy of highly hydrophobic dietary phytochemicals locally in the inflamed colon while minimizing systemic side effects.

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Article information: Apeksha Saraf, Nidhi Dubey, Nitin Dubey, Mayank Sharma, Enhancement of cytotoxicty of diallyl disulfide toward colon cancer by Eudragit S100/PLGA nanoparticles, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102580.