Clearance of intracellular Klebsiella pneumoniae infection using gentamicin-loaded nanoparticles.

Abstract

Klebsiella pneumoniae is a foremost gram-negative pathogen that can induce life-threatening nosocomial pulmonary infections. Although it can be phagocytosed successfully by lung resident macrophages, this pathogen remains viable within vacuolar compartments, resulting in chronic infection and limiting therapeutic treatment with antibiotics. In this study, we aimed to generate and evaluate a cell-penetrant antibiotic poly(lactide-co-glycolide) (PLGA)-based formulation that could successfully treat intracellular K. pneumoniae infection. Screening of formulation conditions allowed the generation of high drug loaded nanoparticles through a water-in-oil-in-water approach. We demonstrated the therapeutic usefulness of these gentamicin-loaded nanoparticles (GNPs), showing their ability to improve survival and provide extended prophylactic protection towards K. pneumoniae using a Galleria mellonella infection model. We subsequently showed that the GNPs could be phagocytosed by K. pneumoniae infected macrophages, and significantly reduce the viability of the intracellular bacteria without further stimulation of pro-inflammatory or pro-apoptotic effects on the macrophages. Taken together, these results clearly show the potential to use antibiotic loaded NPs to treat intracellular K. pneumoniae infection, reducing bacterial viability without concomitant stimulation of inflammatory or pyroptotic pathways in the treated cells.

• Authors: Lai Jiang, Michelle K Greene, Jose Luis Insua, Joana Sa Pessoa, Donna M Small, Peter Smyth, Aidan P McCann, Francesco Cogo, Jose A Bengoechea, Clifford C Taggart, Christopher J Scott
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 279 Pg. 316-325 (06 10 2018) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 29704616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Drug Carriers
• Gentamicins
• Polylactic Acid-Polyglycolic Acid Copolymer

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology)
• Disease Models, Animal
• Drug Carriers (chemistry)
• Gentamicins (administration & dosage, pharmacology)
• Klebsiella Infections (drug therapy)
• Klebsiella pneumoniae (drug effects)
• Macrophages (metabolism)
• Moths (microbiology)
• Nanoparticles
• Phagocytosis (physiology)
• Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)