Search

Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco-regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) microparticles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE%) and in vitro drug release profile. The anti-cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chitosan is a polysaccharide composed of randomly distributed chains of β-(1-4) D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial or total deacetylation of chitin in acidic solution. The chitosan-based hemostatic agents have been gaining much attention in the management of bleeding. The aim of this study was to evaluate in vitro hemagglutination activity of chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles was achieved by ionotropic gelification technique followed by neutralization with NaOH 1 mol/L(-1). The hemagglutination activity was performed on a solution of 2% erythrocytes (pH 7.4 on PBS) collected from five healthy volunteers. The hemolysis determination was made by spectrophotometric analysis. Chitosan nanoparticle solutions without NaOH addition changed the reddish colour of the wells into brown, suggesting an oxidative reaction of hemoglobin and possible cell lysis. All neutralized solutions of chitosan nanoparticles presented positive haemagglutination, without any change in reaction color. Chitosan nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water. Results highlight the need for development of new routes of synthesis of chitosan nanoparticles within human physiologic pH.

Head and neck cancer (HNC) is a complex and heterogeneous disease associated with high mortality and morbidity worldwide. Standard therapeutic management of advanced HNC, which is based on radiotherapy often combined with chemotherapy, has been hampered by severe long-term side effects. To overcome these side effects, tumor-selective nanoparticles have been exploited as a potential drug delivery system to improve HNC therapy. A combination of MEDLINE, EMBASE, Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception up to June 2020 was used for this systematic review. A total of 1747 published manuscripts were reviewed and nine relevant references were retrieved for analysis, while eight of them were eligible for meta-analysis. Based on these studies, the level of evidence about the efficacy of nanoformulation for HNC therapy on tumor response and adverse side effects (SAE) was low. Even though basic research studies have revealed a greater promise of nanomaterial to improve the outcome of cancer therapy, none of them were translated into clinical benefits for HNC patients. This systematic review summarized and discussed the recent progress in the development of targeted nanoparticle approaches for HNC management, and open-up new avenues for future perspectives. [ABSTRACT FROM AUTHOR]