Wednesday, July 27, 2022

PLGA from PolySciTech used in development of inhalable tuberculosis treatment

 


Tuberculosis is a potentially serious infectious disease that mainly affects the lungs. The bacteria that cause tuberculosis are spread from person to person through tiny droplets released into the air via coughs and sneezes. Recently, researchers at Indian Institute of Science used PLGA (cat# AP041) from PolySciTech division of Akina (www.polyscitech.com) to make cationic nanoparticles loaded with rifampicin to target tuberculosis infected mammalian cells. This research holds promise to provide for improved therapies against tuberculosis in the future. Read more: Sharma, Pallavi Raj, Ameya Atul Dravid, Yeswanth Chakravarthy Kalapala, Vishal K. Gupta, Sharumathi Jeyasankar, Avijit Goswami, and Rachit Agarwal. "Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages." Biomaterials Advances 133 (2022): 112612. https://www.sciencedirect.com/science/article/pii/S0928493121007529

“Highlights: Mycobacterium tuberculosis infected macrophages are highly phagocytic. Surface charge of PLGA microparticles modified by conjugating poly-l-lysine. Cationic microparticles were taken up rapidly and in large numbers by macrophages. Rifampicin encapsulation in cationic particles improved its intracellular delivery. Enhanced uptake by immune cells and alveolar macrophages in vivo. Abstract: 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 μm) 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 rifampicin-loaded 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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