Use of outer membrane vesicles (OMVs) for the development of systems facilitating the antibiotic Levofloxacin

Author(s)

Carlos Fernando Macedo da Silva

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Farmacêuticas
• Defense date: 2024-10-31

Examining board members

Marcelo Lancellotti; Paulo Vitor Farago; Angela Faustino Jozala; Marcelo Bispo de Jesus; Paulo Guimarães Gandra

• Advisor: Marcelo Lancellotti

Abstract

The increase in reports of bacterial strains that are multiresistant to antimicrobial therapies has been a major global concern, highlighting the need for the development of new methods to combat these microorganisms. To explore solutions, this project aims to use outer membrane vesicles (OMVs) as carriers for levofloxacin, a fluoroquinolone that acts by inhibiting the enzymatic activity of DNA gyrase and topoisomerase IV, thus blocking the replication machinery of bacterial genetic material, leading to cell death. Throughout this work, several formulations were developed with the goal of associating OMVs with levofloxacin. Among the results obtained, two main formulations stood out: one using constant agitation of the fluid medium, and the other using rotary evaporation. These formulations were tested as treatments on bacterial strains from the LABIOTEC collection, seeking minimum inhibitory concentration doses to evaluate therapeutic efficacy. Additional studies, such as nanovesicle characterization, cytotoxicity assays, and blood-brain barrier testing, were also conducted, comparing the results of OMVs associated and not associated with levofloxacin. The results obtained in this study demonstrated that OMVs are influenced by levofloxacin during their restructuring, causing an increase in nanovesicle size. A synergistic effect occurs with this combination, and the OMVs + Levofloxacin formulation associated by rotary evaporation stands out by showing significantly greater efficacy in inhibiting bacterial growth compared to free antibiotic at the same concentration. These results support the therapeutic potential of OMVs and their possible applications in antimicrobial treatments (AU)

• FAPESP's process: 20/03702-0 - Use of Outer Membrane Vesicles (OMV) for the development of quinolone class antibiotic facilitating systems
• Grantee: Carlos Fernando Macedo da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)