Tuesday, May 1, 2018

PLGA-Rhodamine from PolySciTech used in development of nanoparticles to kill bacteria that hide inside of human cells




Klebsiella pneumoniae is a particularly nasty bacterial strain that can survive being swallowed by a cell and is resistant to traditional antibiotics in this state as the cell protects it from these medicines. This bacteria leads to severe lung infections and can be deadly. Recently, researchers at Queen’s University Belfast used PLGA-Rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) to generate fluorescent-traceable nanoparticles. They tracked the uptake of gentamicin-loaded nanoparticles into cells as a means to treat intra-cellular bacteria. This research holds promise to provide for treatment against this antibiotic-resistant disease. Read more: Jiang, Lai, Michelle K. Greene, Jose Luis Insua, Joana Sa Pessoa, Donna M. Small, Peter Smyth, Aidan McCann et al. "Clearance of intracellular Klebsiella pneumoniae infection using gentamicin-loaded nanoparticles." Journal of Controlled Release (2018). https://www.sciencedirect.com/science/article/pii/S0168365918302244

“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 entrapment 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. Keywords: Gentamicin; PLGA; Nanoparticles; Klebsiella pneumoniae; Intracellular infection; Macrophage; Inflammation; Pyroptosis”

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