Selective Targeting of 4SO4-N-Acetyl-Galactosamine Functionalized Mycobacterium tuberculosis Protein Loaded Chitosan Nanoparticle to Macrophages: Correlation With Activation of Immune System

Abstract

In the present study, we investigated potential of chitosan-based nanoparticles (CNPs) to deliver loaded therapeutic molecules to pathogen harboring macrophages. We fabricated stable CNPs employing ionic cross-linking method and evaluated their potential to target RAW 264.7 cells. The physicochemical characterization of as-synthesized CNPs was determined using electron microscopy, infrared microscopy and zeta potential measurement. Next, cellular uptake and intracellular localization studies of CNPs were followed in living RAW264.7 cells using confocal microscopy. We found that both Acr-1 loaded (CNP-A) and 4-SO4-GalNAc ligand harboring (CNP-L) chitosan nanoparticle experience increased cellular uptake by Mycobacterium smegmatis infected RAW cells. Following cellular digestion in model macrophage cell line (RAW), CNPs provide an increased immune response. Further, 4-SO4-GalNAc bearing CNP-L exhibits high binding affinity as well as antibacterial efficacy toward M. smegmatis. The data of the present study suggest that CNP-based nanoparticle offer a promising delivery strategy to target infected macrophages for prevention and eradication of intracellular pathogens such as M. smegmatis.

Recent Developments in Drug Delivery for Treatment of Tuberculosis by Targeting Macrophages

“…Other types of sugar-based ligands have been reported in the literature, but the lectin-like receptors responsible for targeting were not identified. [182,183] Mubin et.al, decorated chitosan nanoparticles individually with 4SO 4 -N-Acetyl-Galactosamine (4-SO 4 -GalNAc) and Acr-1, a protein of Mtb (Mtb protein). [182] The authors did not encapsulate any drug agent within the chitosan; however, chitosan functionalized with 4-SO 4 -GalNAc exhibited higher binding affinity for macrophages than the bare chitosan particle.…”

“…[182,183] Mubin et.al, decorated chitosan nanoparticles individually with 4SO 4 -N-Acetyl-Galactosamine (4-SO 4 -GalNAc) and Acr-1, a protein of Mtb (Mtb protein). [182] The authors did not encapsulate any drug agent within the chitosan; however, chitosan functionalized with 4-SO 4 -GalNAc exhibited higher binding affinity for macrophages than the bare chitosan particle. Even in the absence of drug, all carriers showed some level of antimicrobial activity.…”

“…In another study, the authors fabricated chitosan nanoparticles and polymeric micelles, and decorated them with hydrolyzed galactomannan to target lectin-like receptors. [182,183] The hydrolyzed galactomannan formulation was internalized effectively by mouse macrophages and resulted in enhanced intracellular concentration of drug within the macrophages.…”