Related Experiment Video
Updated: Aug 7, 2026
Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Intracellular killing of Brucella melitensis in human macrophages with microsphere-encapsulated gentamicin
Concepción Lecároz1, María J Blanco-Prieto, María A Burrell
1Department of Microbiology, University of Navarra, Pamplona, Spain.
Objectives:
Treatment of human brucellosis demands antibiotic targeting into the mononuclear-phagocytic system. The aim of this work was to prepare and characterize particulate carriers containing gentamicin and to study their interactions with phagocytic cells and bactericidal activity against intracellular Brucella melitensis.
Methods:
Different poly(lactide-co-glycolide) (PLGA) polymers with free carboxylic end-group were used to formulate micro- and nanoparticles containing gentamicin, by a water-oil-water solvent-evaporation technique. PLGA 502H and 75:25H microparticles were selected because they showed the highest gentamicin loadings as well as good physico-chemical properties and sustained release in vitro.
Results:
Gentamicin-containing microspheres of both polymers were successfully phagocytosed by infected THP-1 human monocytes, and immunocytochemistry studies revealed that the antibiotic reached Brucella-specific compartments. A dose of 30 microg of encapsulated gentamicin was able to reduce intracellular Brucella infection by 2.2 log.
Conclusions:
Altogether, these results suggest that 502H and 75:25H microspheres are suitable carriers for gentamicin targeting inside human macrophages and thus for brucellosis treatment.
Insights
Poly(lactide-co-glycolide) microspheres effectively deliver gentamicin into macrophages, showing promise for treating brucellosis by targeting intracellular Brucella melitensis.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Infectious Diseases
Background:
- Human brucellosis requires antibiotics that penetrate the mononuclear-phagocytic system.
- Effective intracellular delivery of gentamicin is crucial for treating Brucella infections.
Purpose of the Study:
- To create and evaluate poly(lactide-co-glycolide) (PLGA) micro- and nanoparticles loaded with gentamicin.
- To assess the interaction of these carriers with phagocytic cells.
- To determine the bactericidal efficacy against intracellular Brucella melitensis.
Main Methods:
- Utilized a water-oil-water solvent-evaporation technique to formulate gentamicin-loaded PLGA microparticles.
- Employed PLGA 502H and 75:25H polymers for their high gentamicin loading and sustained release properties.
- Investigated phagocytosis by infected THP-1 human monocytes and immunocytochemistry for antibiotic localization.
Main Results:
- Successfully developed gentamicin-loaded PLGA microspheres (502H and 75:25H).
- Demonstrated phagocytosis of microspheres by infected human monocytes (THP-1 cells).
- Confirmed gentamicin localization within Brucella-specific compartments and a 2.2 log reduction in intracellular bacteria.
Conclusions:
- PLGA 502H and 75:25H microspheres are effective carriers for gentamicin.
- These microspheres facilitate targeted delivery of gentamicin into human macrophages.
- The developed microspheres show potential for improved brucellosis treatment.
