Letícia D.M. Carrasco, Hadassa C.A.S. Santos, Jorge L.M. Sampaio and Ana M. Carmona-Ribeiro* Pages 39 - 47 ( 9 )
Background and Objective: Nanoparticles (NPs) have been recognized as important drug delivery agents in several instances including the delivery of antibiotics against intracellular pathogenic microorganisms. In this work the activity of self-assembled nanoparticles (NPs) of clarithromycin (CLA), cationic lipid and polyelectrolytes against important mycobacteria such as Mycobacterium abscessus is evaluated.Methods: NPs from injection of a CLA/cationic lipid ethanol solution in aqueous carboxymethylcellulose (CMC) solution followed or not by the addition of poly (diallyldimethylammonium chloride) (PDDA) to the anionic CLA/cationic lipid/CMC NPs were characterized by dynamic light scattering for sizing, zeta-potential and polydispersity, scanning electron microscopy (SEM) for morphology, colloidal stability along time from sizing and macroscopic observation, inhibitory activity against mycobacteria from determination of minimal inhibitory concentrations (MIC), toxicity against macrophages in culture from determinations of macrophages viability and inhibition of mycobacterial growth in biofilms. Results: Anionic CLA/cationic lipid/CMC NPs incorporated higher percentage of CLA than the cationic CLA/cationic lipid/CMC/PDDA NPs and showed higher antimicrobial activity against M. abscessus and lower toxicity to macrophages than the cationic NPs. Conclusion: These findings opened the possibility of extending the incorporation of other lipophilic antibiotics or drugs into the here described self-assembled NPs and showed NPs adequacy to deliver antibiotics and drugs intracellularly for sustained release inside cells and activity against biofilms growth.
Nanoparticles of lipophilic antibiotic, cationic lipid and polyelectrolytes, clarithromycin, mycobacteria, intracellular bacteriostatic and cytotoxic effect, inhibition of biofilm growth.
Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Av Prof. Lineu Prestes 748, CEP 05508-000, Sao Paulo SP, Departamento de Analises Clínicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, CEP 05508-900, Sao Paulo, Departamento de Analises Clínicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, CEP 05508-900, Sao Paulo, Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-000, Sao Paulo SP