Journal
BIOMATERIALS ADVANCES
Volume 133, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2021.112612
Keywords
Cell-particle interaction; Microparticle drug delivery; Phagocytosis; Alveolar macrophages
Categories
Funding
- Department of Science and Technology (DST, India) Ramanujan Fellowship [SB/S2/RJN-036/2017]
- Bill & Melinda Gates Foundation [OPP1210498]
- Department of Biotechnology (DBT, India) Junior Research Fellowship program [DBT/2017/IISc/941]
- Bill and Melinda Gates Foundation [OPP1210498] Funding Source: Bill and Melinda Gates Foundation
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Inhalable microparticle-based drug delivery platforms are being extensively studied for Tuberculosis treatment. The physical parameters of microcarriers and their interaction with Mycobacterium tuberculosis infected cells have been explored in this study. The results show that cationic particles improve the uptake of microparticles by infected cells and enhance the anti-bacterial function of the drug.
Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5-2 mu m) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and led to enhanced anti-bacterial function when compared to non-modified rifampicinloaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells.
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