Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection

Sharif M Abdelghany1, Derek J Quinn, Rebecca J Ingram

  • 1School of Pharmacy, Queen's University Belfast, UK.

Insights

Researchers developed controlled-release gentamicin nanoparticles using PLGA to improve treatment for Pseudomonas infections. This formulation demonstrated sustained drug release and enhanced antimicrobial efficacy in vitro and in vivo.

Area of Science:

  • Biomedical Engineering
  • Pharmacology
  • Infectious Diseases

Background:

  • Gentamicin is an essential aminoglycoside antibiotic for Pseudomonas infections.
  • Its clinical utility is constrained by a short half-life, necessitating frequent dosing.
  • Developing sustained-release formulations is crucial for improved therapeutic outcomes.

Purpose of the Study:

  • To engineer poly(lactide-co-glycolide) (PLGA) nanoparticles for controlled gentamicin release.
  • To optimize drug entrapment within the PLGA matrix.
  • To evaluate the in vitro and in vivo efficacy of the gentamicin-PLGA nanoparticles against Pseudomonas aeruginosa.

Main Methods:

  • Fabrication of PLGA nanoparticles encapsulating gentamicin.
  • Optimization of drug entrapment by adjusting formulation pH.
  • In vitro drug release studies over 16 days.
  • Antimicrobial testing against planktonic and biofilm P. aeruginosa PA01.
  • In vivo evaluation in a 96-hour murine peritoneal infection model.

Main Results:

  • Achieved high gentamicin entrapment efficiency (up to 22.4 μg/mg PLGA) by increasing formulation pH.
  • Demonstrated sustained gentamicin release from PLGA nanoparticles for up to 16 days.
  • Showed significantly enhanced antimicrobial activity in vivo, reducing bacterial load and inflammatory markers (interleukin-6, myeloperoxidase) compared to free gentamicin.

Conclusions:

  • PLGA nanoparticles provide an effective platform for controlled gentamicin delivery.
  • This formulation significantly improves therapeutic efficacy against Pseudomonas infections in a murine model.
  • Controlled-release gentamicin holds promise for managing challenging Pseudomonas infections.