Preparation of Curdlan sulphate - Chitosan nanoparticles as a drug carrier to target Mycobacterium smegmatis infected macrophages.

Abstract

In this study, curdlan sulphate - chitosan nanoparticles were prepared through polyelectrolyte complexing at a mass ratio of 2:1 respectively. The curdlan was produced by fermentation with Agrobacterium sp. ATCC 31750, which was then sulphated to form the polyanionic polymer. A first-line tuberculosis drug, Rifampicin and a phytochemical, DdPinitol, were encapsulated into Curdlan Sulphate (CS) - Chitosan Nanoparticles (C) (CSC NPs) of size 205.41 ± 7.24 nm. The drug release kinetics followed a Weibull model with initial burst release (48 % Rifampicin and 27 % d-Pinitol within 6 h), followed by a sustained release. The prepared CSC: d-PIN + RIF NPs was cytocompatible and entered the M.smegmatis infected macrophages through multiple endocytic pathways including clathrin, caveolae and macropinocytosis. They showed superior bactericidal activity (2.4-2.7 fold) within 4 h when compared to free drug Rifampicin (1.6 fold). The drug encapsulated CSC: RIF suppressed the pro-inflammatory gene (TNF-α by 3.66 ± 0.19 fold) and CSC: d-PIN + RIF increased expression of the anti-inflammatory gene (IL-10 by 13.09 ± 0.47 fold). Expression of TGF- β1 gene also increased when treated with CSC: d-PIN + RIF (13.00 ± 0.19 fold) which provided the immunomodulatory activity of the encapsulated CSC NPs. Thus, curdlan sulphate - chitosan polyelectrolyte complex can be a potential nanocarrier matrix for intracellular delivery of multiple drugs.

• Authors: Radhika Ravindran, Kartik Mitra, Senthil Kumar Arumugam, Mukesh Doble
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 258 Pg. 117686 (Apr 15 2021) ISSN: 1879-1344 [Electronic] England
• PMID: 33593559 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Ltd.

Chemical References

• Drug Carriers
• Polyelectrolytes
• Polymers
• beta-Glucans
• chitosan sulfate
• polyanions
• curdlan
• Chitosan
• curdlan sulfate
• Rifampin

Topics

• Animals
• Cell Survival
• Chitosan (chemistry)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Liberation
• Endocytosis
• Hydrogen-Ion Concentration
• Inflammation
• Kinetics
• Macrophages (drug effects, metabolism, microbiology)
• Mice
• Mycobacterium Infections, Nontuberculous (drug therapy)
• Mycobacterium smegmatis (drug effects)
• Nanoparticles (chemistry)
• Polyelectrolytes (chemistry)
• Polymers (chemistry)
• RAW 264.7 Cells
• Rifampin (pharmacology)
• beta-Glucans (chemistry)