Polyphenol-crosslinked green synthesis of mucoadhesive chitosan nanoparticle encapsulated with cisplatin for localized management of cervical cancer.

Chitosan (CS) nanoparticles have been widely investigated for cervical cancer (CC) therapy, with tripolyphosphate (TPP) commonly used as a crosslinker. This study explored ellagic acid (EA), a natural polyphenol with anticancer activity, as an alternative crosslinker for cisplatin-loaded EA-crosslinked CS nanoparticles (CisEANP) and compared them with cisplatin-loaded TPP-crosslinked CS nanoparticles (CisTPPNP). CisEANP showed a particle size (PS) of 260.9 ± 4.40 nm and zeta potential of +35 ± 1.30 mV, with spherical morphology and good mucoadhesiveness suitable for vaginal administration. Both formulations provided sustained cisplatin (Cis) release, with higher drug release from CisEANP. CisEANP significantly reduced HeLa cell viability compared with CisTPPNP and showed increased reactive oxygen species (ROS) generation and caspase activation. Antiangiogenic activity was confirmed by the chorioallantoic membrane (CAM) assay. In an Ehrlich ascites carcinoma (EAC)-induced CC mouse model, CisEANP and CisTPPNP reduced tumor volume by 1.23- and 1.49-fold, respectively, compared with disease control, with greater tumor regression observed for CisEANP. Histopathology supported the therapeutic findings, while X-ray imaging confirmed vaginal retention for up to 8 h. Overall, EA showed potential as a functional crosslinker for localized cisplatin delivery in CC.