A novel mucoadhesive phytic acid grafted chitosan nanocarrier encapsulated with cisplatin for site-specific cervical cancer therapy: <i>in vitro</i> and <i>in vivo</i> assessments

A mucoadhesive vaginal drug delivery system offers a promising strategy to mitigate chemotherapy-associated systemic toxicity in cervical cancer (CC). Metalloenzymes like superoxide dismutase 2 (SOD2) and catalase are responsible for maintaining oxidant–antioxidant balance in cancer cells. The present study proposed a new approach to prepare cisplatin-loaded phytic acid crosslinked chitosan nanoparticles (CisPANP). CisPANP exhibited a particle size (PS) of 278.24 ± 15.64 nm with a zeta potential of +39 ± 2.46 mV. The nanoparticles demonstrated a sustained drug release behaviour, i.e. 86.85 ± 6.38% drug was released in 24 h. CisPANP were observed to significantly downregulate the expression of SOD and catalase by 3.5 and 1.7-fold, respectively, as compared to untreated cells. CisPANP further increased ROS level and inhibited HeLa cell viability. The <i>in vivo</i> anti-cancer efficacy of CisPANP was evaluated in EAC cell line-induced CC mice model. The tumour volume in CisPANP was significantly reduced as compared to pure cisplatin (pure Cis). CisPANP was well-retained making Cis available in the vagina. From the histopathology, significant adverse effects were not observed in the surrounding tissue of tumour treated with CisPANP, indicating its safety. From the observations of the present investigation, CisPANP could serve as a potential candidate for the localised treatment of CC. PA, as a crosslinker, was able to alter metalloenzyme expression.CisPANP revealed superior anticancer potential than CisTPPNP.PA could successfully add to the anti-cancer benefits of Cis in CisPANP. PA, as a crosslinker, was able to alter metalloenzyme expression. CisPANP revealed superior anticancer potential than CisTPPNP. PA could successfully add to the anti-cancer benefits of Cis in CisPANP.