The present study is designed to evaluate the nanotherapeutic efficacy of prepared PLGA-loaded Nedaplatin (PLGA-NDP) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced experimental oral carcinogenesis in hamster buccal pouch (HBP) model. The buccal pouch of golden Syrian hamsters was painted with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, ultimately leading to the development of oral squamous cell carcinoma (OSCC). Oral administration of PLGA-NDP (Pre-initiation) and Cisplatin delivery (5mg/kg b.wt) started one week before the carcinogen exposure and continued on alternative days. Post-administration of PLGA-NDP (5 mg/kg b.wt) started 2 days after carcinogen (DMBA) induction until the end of the experiment. After the 14 th week, we observed that DMBA-painted hamsters exhibited tumour formation, morphological alterations, and well-differentiated OSSC in addition to the responsive molecular proteins during oral carcinogenesis. Furthermore, immunoblotting analysis demonstrated that PLGA-NDP inhibits Notch signalling, as evidenced by downregulation of Bcl-Xl, Bcl-2, p21, PGE2, HGF, and CXCL12 proteins, and upregulation of p53 and Bax. This apoptotic response is crucial for PLGA-NDP to induce apoptosis. In addition, RT-PCR results showed that PLGA-NDP nanoparticles play a down-regulatory role in the therapeutic action of the notch signalling gene (Notch1, Notch 2, Hes1, Hey1, and Jagged1) at the mRNA transcription level in HBP carcinoma. Taken together, these data indicate that PLGA-NDP is a potent inhibitor of oral carcinogenesis and the expansion of cells that specifically target the Notch signalling pathway indicates that obstructing Notch signalling could potentially serve as a new and innovative therapeutic approach for oral squamous cell carcinoma (OSCC).

Poly- (D, L-lactic-co-glycolic) acid-loaded nedaplatin nanoparticles (PLGA-NDP) have been used to treat oral squamous cell carcinoma (OSCC). The preparation and characterisation of PLGA-NDP, which was formed and optimised using the double emulsion technique and Box-Behnken design, were investigated in detail. Various methods, including scanning electron microscopy- energy dispersive X-ray spectroscopy, dynamic light scattering, thermogravimetric analysis-differential thermal analysis, Fourier-Transform Infrared Spectroscopy, UV-VIS spectroscopy, and in vitro drug release studies, were employed to examine the morphology, element distribution, physical state, internal structure, encapsulation efficiency, and release profile of the nanoparticles. The Box-Behnken design, which used four factors at four levels to calculate the central point, significantly improved the results. The response of the optimised condition provided an accurate prediction, and the experiment was conducted further. The design was validated, and satisfactory agreement was observed between the predicted and experimental values. The obtained results provided evidence of a new geometric construction of PLGA-loaded Nedaplatin nanoparticles with enhanced efficiency when analysed through bio-assessment, such as cytotoxicity measurement, intracellular ROS, mitochondrial dysfunction, colony formation, apoptosis-associated gene expression profile, and cell cycle analysis in OECM-1 cell lines. Therefore, these findings and techniques are useful for the development of PLGA-NDPs.