PLGA Microparticles Enriched with Linezolid and Moxifloxacin Nanoparticles via Spray drying Applied to Inhalation Treatment of Mycobacterium tuberculosis Infections

• Grant number: 24/08933-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Larissa Sposito
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Infections caused by Mycobacterium tuberculosis (MTB), also known as Koch's bacillus, are a global concern and deserve special attention as they primarily affect the lungs but can also target other organs and systems. The ability of MTB to infiltrate macrophages and fibroblasts for protection increases its resistance to conventional antimicrobials. In this context, there is growing interest in finding new substances and strategies to treat MTB. Developing an inhalable polymeric system using nanoparticles of linezolid and moxifloxacin incorporated into PLGA microparticles shows promise as an inhalation strategy, aiming to direct active substances to the pulmonary region and combat MTB infections. Chitosan nanoparticles coated with mannose, containing linezolid and moxifloxacin, will be characterized for their average hydrodynamic diameter, polydispersity index, zeta potential, particle concentration, and morphology. Encapsulation efficiency and in vitro drug release profile assays will also be performed. Subsequently, the nanoparticles will be incorporated into PLGA microparticles and evaluated for important characteristics for their potential application, such as mucoadhesiveness, powder characterization, and in vitro pulmonary deposition profile. Additionally, antimicrobial, cytotoxic, and intramacrophagic activity will be assessed in vitro, as well as anti-MTB activity in vivo. It is expected to develop a stable and effective inhalation system against MTB.