Development and characterization of chitosan/dextran sulfate nanoparticles for subsequent incorporation into inhalation carriers as a strategy for pulmonary release of antibiotics in the treatment of tuberculosis

• Grant number: 24/10660-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2024
• Effective date (End): September 30, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Andréia Bagliotti Meneguin
• Grantee: Bárbara de Araujo Barbieri
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis (TB) is a contagious respiratory disease caused by the bacterium Mycobacterium tuberculosis, capable of infecting alveolar macrophages. The current treatment combines antibiotics such as rifampicin (RIF), isoniazid, pyrazinamide and ethambutol, administered orally for at least six months. The long treatment period, high doses of drugs needed to reach the site of infection and the adverse effects caused, such as hepatotoxicity, are among the main obstacles to treatment efficacy, in addition to pulmonary granulomas, lipophilic structures generated by the host that harbor M. tuberculosis in an attempt to contain the infection which hinders the penetration and proper distribution of drugs. Nanotechnology emerges as an innovative alternative for the targeted release of anti-tuberculosis drugs inside granulomas. The cationic nature of chitosan (QS) allows the formation of nanostructured polyelectrolyte complexes with anionic polymers, such as dextran sulfate (SD), and the interest in using rifampicin for intra-granuloma release is due to its penetration efficiency into pulmonary lesions and progressive accumulation capacity inside caseum, maintaining therapeutic concentrations throughout the dosing interval. The aim of the study is to develop and characterize polymeric nanoparticles (NPs) of QS/SD loaded with RIF. The NPs will be obtained by the polyelectrolyte complexation technique using a total polymer concentration of 0.5 mg mL1, with QS/SD ratios (w/v) of 1:9, 3:7, 5:5, 7:3 and 9:1. Particle size, Polydispersity Index (PdI), and Zeta Potential (PZ) will be analyzed using the Zetasizer Nano-ZS®. This NP system for pulmonary release emerges as an innovative therapeutic strategy for TB treatment efficacy, aiming to minimize adverse effects, avoid first-pass metabolism, and overcome the physical and biological barriers associated to pulmonary granulomas.