Related Experiment Video
Updated: Jul 17, 2026
Galleria mellonella as an Antimicrobial Screening Model
Published on: October 11, 2024
Poly(D,L-lactide-coglycolide) particles containing gentamicin: pharmacokinetics and pharmacodynamics in Brucella
M C Lecaroz1, M J Blanco-Prieto, M A Campanero
1Department of Microbiology, University of Navarra, Irunlarrea 1, 31080 Pamplona, Spain.
Abstract:
Drug delivery systems containing gentamicin were studied as a treatment against experimental brucellosis in mice. Micro- and nanoparticles prepared by using poly(D,L-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H were successfully delivered to the liver and the spleen, the target organs for Brucella melitensis. Both polymers have the same molecular weight but have different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and 75:25H released their contents in a sustained manner, in contrast to PLGA 502H nanoparticles, which were degraded almost completely during the first week postadministration. The values of the pharmacokinetic parameters after administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded gentamicin revealed higher areas under the curve (AUCs) for the liver and the spleen and increased mean retention times (MRTs) compared to those for the free drug, indicating the successful uptake by phagocytic cells in both organs and the controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H microparticles presented similar pharmacokinetic parameter values for the liver, but those made of PLGA 75:25 H were more effective in targeting the antibiotic to the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg significantly reduced the load associated with the splenic B. melitensis infection. Thus, the formulation made with the 75:25H polymer was more effective than that made with 502H microspheres (1.45-log and 0.45-log reductions, respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and pharmacodynamic parameters showed the suitability of 75:25H microspheres to reduce the infection of experimentally infected mice with B. melitensis.
Insights
Poly(D,L-lactide-coglycolide) (PLGA) microspheres effectively deliver gentamicin to target organs for brucellosis treatment in mice. The PLGA 75:25H formulation demonstrated superior efficacy in reducing splenic bacterial load compared to PLGA 502H.
Area of Science:
- Biomaterials Science
- Pharmacology
- Infectious Diseases
Background:
- Brucellosis, caused by Brucella melitensis, is a significant zoonotic infection.
- Effective drug delivery systems are crucial for treating intracellular bacterial infections targeting organs like the liver and spleen.
- Poly(D,L-lactide-coglycolide) (PLGA) is a biodegradable polymer widely used in drug delivery systems.
Purpose of the Study:
- To evaluate gentamicin-loaded PLGA micro- and nanoparticles as a drug delivery system for experimental brucellosis in mice.
- To compare the efficacy of different PLGA formulations (502H and 75:25H) in targeting gentamicin to the liver and spleen.
- To assess the pharmacokinetic and pharmacodynamic profiles of gentamicin delivered via PLGA systems.
Main Methods:
- Preparation of gentamicin-loaded PLGA microparticles and nanoparticles using PLGA 502H and PLGA 75:25H polymers.
- Intravenous administration of drug-loaded systems to mice infected with Brucella melitensis.
- Pharmacokinetic analysis, including area under the curve (AUC) and mean retention time (MRT), in liver and spleen.
- Evaluation of therapeutic efficacy by measuring bacterial load reduction in the spleen.
Main Results:
- PLGA micro- and nanoparticles successfully delivered gentamicin to the liver and spleen.
- PLGA 502H and 75:25H microparticles exhibited sustained gentamicin release, while PLGA 502H nanoparticles showed rapid degradation.
- Gentamicin-loaded PLGA microspheres resulted in higher AUCs and MRTs in the liver and spleen compared to free gentamicin.
- PLGA 75:25H microspheres demonstrated superior targeting to the spleen and a more significant reduction in splenic Brucella melitensis load (1.45-log) compared to PLGA 502H microspheres (0.45-log) after three doses.
Conclusions:
- Gentamicin-loaded PLGA microspheres are effective drug delivery systems for treating experimental brucellosis in mice.
- The PLGA 75:25H formulation exhibits enhanced pharmacokinetic and pharmacodynamic properties, making it a promising candidate for brucellosis therapy.
- Sustained release and targeted delivery to the spleen by PLGA 75:25H microspheres are key to its improved therapeutic efficacy.
More Related Videos
09:17A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
Published on: January 2, 2017
11:32Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
