Polymyxin B Loaded Poly Lactic-Co-Glycolic Acid Nanoparticles Retains Antimicrobial Activity and Reduces Kidney Cells Damage

Author(s)

de Jesus, Teixeira Alison ; Lupeti, de Cena Gabrielle ; Martins, Andrade Vitor ; Silva, Carvalho Isabel Chaves ; Delfino, Pedreca Maria Goretti ; Ferreira, Macedo Erenilda ; Batista, Tada Dayane ; Katia, Conceicao

• Document type: Journal article
• Source: BIONANOSCIENCE; v. 15, n. 1, p. 13-pg., 2025-03-01.

Abstract

Polymyxin B (polyB) is a lipopeptide used as a last-line treatment against antibiotic-resistant Gram-negative bacteria. However, the application of polyB is limited by expressive nephrotoxicity. So, encapsulation of peptides into nanoparticles has been a tool to circumvent toxicity problems. Polymeric nanoparticles have been prepared with poly (lactic-co-glycolic acid), PLGA, a biodegradable polymer that allows the controlled release of drugs, increasing their selectivity and making them less toxic to adjacent tissues. PLGA nanoparticles were synthesized by nanoprecipitation and characterized by dynamic light scattering. PolyB was encapsulated as a free form and also linked to a dansyl fluorescent probe to be quantified. Antimicrobial assays were carried out in Escherichia coli and Pseudomonas aeruginosa. Hemolysis was evaluated with human red blood cells. In vitro cytotoxicity was evaluated against LLC-PK and CMHI kidney cells. In vivo studies were carried out in the Galleria mellonella infection model. PolyB-PLGA nanoparticles exerted bactericidal action against E. coli and P. aeruginosa at 11.8 mu g/mL and showed no hemolytic activity. PolyB-PLGAs did not promote cellular viability decrease in renal cells. In vivo tests with G. mellonella indicated that in addition to not showing toxicity, the nanosystem inhibited disease progression on larvae infected by E. coli. (AU)

• FAPESP's process: 21/04316-9 - Design and characterization of bioactive hybrid peptides for therapeutic application and functionalization with nanoparticles
• Grantee: Katia da Conceição
• Support Opportunities: Regular Research Grants