QbD Manoeuvred Niclosamide Laden Polylactic-co-Glycolic Acid Nanoparticles-Impregnated Gelatin Nanofibers for the Management of Oral Carcinoma

Oral carcinoma (OC) is the leading cause of mouth deformation and mortality in the world. It is the 6th most frequent cancer globally. OC is aggressive cancer-forming tumors that invade nearby tissues, leading to locoregional spread. Surgical ablation of large tumors leads to removal of a large chunk of the mouth leading to loss of function and aesthetics. Hence, the use of neoadjuvant and adjuvant chemotherapy is common for the shrinking of tumors and the prevention of tumor recurrence. In this research, we have developed niclosamide (NIC)-loaded nanoparticles-impregnated gelatin nanofibers (NNPF) for local action. The developed nanoparticles demonstrated superior cytotoxicity in the oral cancer cell line compared to the free drug. Cell staining studies demonstrated increased apoptosis and reactive oxygen species generation after treatment with NIC-loaded nanoparticles (NNP). Cell cycle analysis demonstrated cell cycle inhibition in the G0/G1 phase. Cytotoxicity studies in 3D tumoroids demonstrated the ability of NNP to prevent cancer cell growth in 3D arrangement. Thus, NNPF could prove to be a boon for localized delivery as implant-based systems for sustained release in various cancer therapeutic applications.