Liposome-siderophore conjugates loaded with moxifloxacin serve as a model for drug delivery against Mycobacterium tuberculosis

Author(s):Show less -

Ribeiro, Camila Maringolo ; Roque-Borda, Cesar Augusto ; Franzini, Maria Carolina ; Manieri, Karyn Fernanda ; Demarqui, Fernanda Manaia ; Campos, Debora Leite ; Machado, Rachel Temperani Amaral ; da Silva, Isabel Cristiane ; Luiz, Marcela Tavares ; Di Filippo, Leonardo Delello ; da Silva, Patricia Bento ; da Rocha, Marcia Cristina Oliveira ; Bao, Sonia Nair ; Masci, Domiziana ; Fernandes, Guilherme F. S. ; Castagnolo, Daniele ; Chorilli, Marlus ; Pavan, Fernando Rogerio

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 655, p. 14-pg., 2024-03-28.

Abstract

Tuberculosis (TB) is an infectious disease that annually affects millions of people, and resistance to available antibiotics has exacerbated this situation. Another notable characteristic of Mycobacterium tuberculosis, the primary causative agent of TB, is its ability to survive inside macrophages, a key component of the immune system. In our quest for an effective and safe treatment that facilitates the targeted delivery of antibiotics to the site of infection, we have proposed a nanotechnology approach based on an iron chelator. Iron chelators are the primary mechanism by which bacteria acquire iron, a metal essential for their metabolism. Four liposomes were synthesized and characterized using the dynamic light scattering technique (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). All of these methods revealed the presence of spherical particles, approximately 200 nm in size. NTA indicated a concentration of around 1011 particles/mL. We also developed and validated a high-performance liquid chromatography method for quantifying Moxifloxacin to determine encapsulation efficiency (EE) and release profiles (RF). The EE was 51.31 % for LipMox and 45.76 % for LipIchMox. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the phagocytosis of liposomal vesicles by macrophages. Functionalizing liposomes with iron chelators can offer significant benefits for TB treatment, such as targeted drug delivery to intracellular bacilli through the phagocytosis of liposomal particles by cells like macrophages. (AU)

• FAPESP's process: 23/01664-1 - Synthesis and characterization of antimicrobial peptide "B1CTcu5" analogs encapsulated in colon-specific microparticles and in vitro an in vivo studies against Mycobacterium tuberculosis
• Grantee: Fernando Rogério Pavan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04793-9 - Liposomes containing moxifloxacin: cytotoxicity, permeability in intestinal cells, electron microscopy and micronucleus
• Grantee: Maria Carolina Franzini
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/13497-4 - Search for the mechanism of action and therapeutic effect of new classes of drugs against Mycobacterium tuberculosis
• Grantee: Fernando Rogério Pavan
• Support Opportunities: Regular Research Grants