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Dual pH-Responsive Macrophage-Targeted Isoniazid Glycoparticles for Intracellular Tuberculosis Therapy

With the support of the Wellcome-Translational Partnership, the teams of Dr Meera Unnikrishnan and Professor Sebastien Perrier have developed a new family of nanoparticles for the treatment of TB infection which address the main shortfall of current therapies, poor penetration to mycobacterium containing niches such as macrophages.

The team has designed mannose-decorated nanoparticles loaded with a well-established TB drug, which can degrade and deliver their payload at lysosomal pH. Fluorescence uptake studies showed preferential endocytosis of mannosylated particles via sugar-lectin interactions, and the particles were also shown to be effective at killing intracellular M. bovis BCG bacteria in THP-1 macrophages. Taken together these results show that in vitro, such macrophage-targeted particles increase intracellular isoniazid concentration, showing an increased antimicrobial activity against intracellular mycobacteria. Read the paper here

Fri 06 Aug 2021, 15:07 | Tags: BMS