Following systemic application, the treatments before reaching maximal therapeutic effect at the target tissue, they must pass through complex environments and biological barriers as passing through the systemic vasculature, absorption, and retention within the epithelium, diffusion from blood vessels to the underneath tissue, and perfusion through the spaces between the epithelium and the basement membrane. Aggressive chemotherapeutic agents have drastic side effects on the patients 2, 3. New updates in medicine have been raging a war on cancer for a long time and despite great improvement in this field, cancer still devastates a lot of lives each year 1. Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X 2 = 12.63, P < 0.001). Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. FTIR peaks identified the polymeric structure of the drug nano-carrier. The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). A targeted anticancer drug (Cetuximab) and chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. The induced tumors were examined by needle biopsy. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients.
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