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

Autor: Jiang L; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Greene MK; Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Insua JL; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Pessoa JS; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Small DM; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Smyth P; Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., McCann AP; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Cogo F; Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Bengoechea JA; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Taggart CC; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK., Scott CJ; Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK. Electronic address: c.scott@qub.ac.uk.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2018 Jun 10; Vol. 279, pp. 316-325. Date of Electronic Publication: 2018 Apr 25.
DOI: 10.1016/j.jconrel.2018.04.040
Abstrakt: 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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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