TOXICITY AND ANTI-INFLAMMATORY EVALUATION OF CHITOSAN NANOPARTICLES LOADED QITH SOTAGLIFLOZIN IN PLATELETS AND NEUTROPHILS

• Grant number: 25/15772-6
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: November 01, 2025
• End date: January 31, 2026
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Dayane Batista Tada
• Grantee: Giovana dos Santos Barreto
• Supervisor: Jason Knight
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated to the scholarship: 24/08838-8 - Synthesis of chitosan nanoparticles for encapsulation of antidiabetic drugs, BP.IC

Abstract

Diabetes Mellitus (DM) is a metabolic disorder characterized by alterations in glucose homeostasis, affecting millions of people worldwide. The treatment of type 2 diabetes mellitus (DMT2) involves lifestyle changes and the use of antidiabetic medication, such as oral hypoglycemic agents and ¿-glucosidase inhibitors. Recently, Sodium-Glucose Cotransporter (SGLT) inhibitors, such as Sotagliflozin, have been investigated for their ability to reduce glucose reabsorption by the kidneys and influence cardiac receptors, demonstrating benefits in heart failure. However, their use may lead to adverse effects, including diabetic ketoacidosis (DKA), due to increased utilization of fatty acids as an energy source and consequent production of ketone bodies.Nanotechnology emerges as an alternative to improve the efficiency and safety of antidiabetic drugs, with particular emphasis on polymeric nanoparticles (NPs). Chitosan, a natural polymer, has been explored for its biocompatibility, renal targeting ability, and antimicrobial properties. In addition to evaluating the cellular cytotoxicity of the drug delivery system, it is necessary to assess whether it presents platelet toxicity. Furthermore, the interaction between the immune system and NPs is crucial, as neutrophils may respond by releasing extracellular traps (NETs), which, although involved in pathogen defense, are also associated with chronic inflammation and autoimmunity. Therefore, evaluating neutrophil activation and NET formation is essential to understand the impacts of the Sotagliflozin nanoencapsulated chitosan delivery system, enabling its development as an innovative approach for DMT2 treatment. (AU)