Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages

Sharma, PR and Dravid, AA and Kalapala, YC and Gupta, VK and Jeyasankar, S and Goswami, A and Agarwal, R (2021) Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages. In: Materials Science and Engineering C .

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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. © 2021 Elsevier B.V.

Item Type:	Journal Article
Publication:	Materials Science and Engineering C
Publisher:	Elsevier Ltd
Additional Information:	The copyright for this article belongs to the Author.
Keywords:	Amino acids; Antigen-antibody reactions; Bone; Controlled drug delivery; Cytology; Mammals; Particle size analysis; Targeted drug delivery, Alveolar macrophages; Cationics; Cell-particle interaction; In-vitro; Infected cells; Inhalable particles; Micro particles; Microparticle drug delivery; Mycobacterium tuberculosis; Poly-L-Lysine, Macrophages
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	07 Jan 2022 07:01
Last Modified:	07 Jan 2022 07:01
URI:	http://eprints.iisc.ac.in/id/eprint/70950

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