[Fe(phen) 3 ] 2+ and [Fe(phen) 3 ] 2+ -Loaded Nanostructured Lipid System: In Silico, In Vitro, and In Vivo Efficacy against Mycobacterium tuberculosis
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), remains one of the leading causes of mortality from infectious diseases worldwide. So, this study investigates the antimicrobial potential of [Fe(phen) 3 ] 2+ (FEP) and FEP-loaded nanostructured lipid systems (NLS@FEP) as an innovative therapeutic approach for TB. The FEP showed promising antimycobacterial activity in simulated physiological environments, with minimum inhibitory concentrations (MIC 90 ) from 3.92 to 0.98 μg mL –1 . FEP combination with rifampicin or pretomanid significantly reduced the MIC 90, with fractional inhibitory concentration index (FICI) of 0.27 and 0.103, respectively. Field emission scanning electron microscopy (FE-SEM) analysis revealed significant structural alterations in the Mtb cell wall, suggesting that FEP interferes with its synthesis. In silico analyses and whole-genome sequencing (WGS) supported these findings, identifying mutations in key genes, such as ponA1, which encodes a penicillin-binding protein involved in peptidoglycan synthesis. In silico modeling predicted high FEP affinity for PonA1, in line with FE-SEM observations; however, these predictions are hypothesis-generating and require functional validation. FEP-loaded nanostructured lipid system (NLS@FEP) was designed to optimize FEP activity, which improved its stability and bioavailability. In a murine model infected with Mtb H37Rv, free FEP and NLS@FEP achieved complete elimination of pulmonary infection.
Source: ACS Omega
Authors: Fernanda Manaia Demarqui, Christian Shleider Carnero Canales, Rachel Temperani Amaral Machado, Rafael Miguel Sábio, Ingrid Gracielle M. Silva, Karine B. Barros-Cordeiro, Sônia N. Báo, Masanori Asai, Sandra M. Newton, Paul R. Langford, Fernando Rogério Pavan
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funders: Universidade de Brasília, Imperial College London, National Centre for the Replacement, Refinement and Reduction of Animals in Research, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade Estadual Paulista, Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council
Awards: G1207375514, G1947320798, G22113365, G3699860204, G3820808591, Brazil-Imperial College collaboration: small RNAs in A. pleuropneumoniae - from identification to application, G4156952298, G6289349112, G6397617836, Synthesis and characterization of antimicrobial peptide ""B1CTcu5"" analogs encapsulated in colon-specific microparticles and in vitro an in vivo studies against Mycobacterium tuberculosis, G7942132238, G8445122136, G880097641
OpenAlex ID: W7106799474