Dry Powder Comprised of Isoniazid-Loaded Nanoparticles of Hyaluronic Acid in Conjugation with Mannose-Anchored Chitosan for Macrophage-Targeted Pulmonary Administration in Tuberculosis

Abstract

Marketed dosage forms fail to deliver anti-tubercular drugs directly to the lungs in pulmonary Tuberculosis (TB). Therefore, nanomediated isoniazid (INH)-loaded dry powder for inhalation (Nano-DPI) was developed for macrophage-targeted delivery in TB. Mannosylated chitosan (MC) and hyaluronic acid (HA) with an affinity for the surface mannose and CD44 receptors of macrophages were used in conjugation to prepare hybrid nanosuspension by ionic gelation method using cross-linker, sodium tri-polyphosphate (TPP) followed by freeze-drying to obtain a dry powder composed of nanoparticles (INH-MC/HA NPs). Nanoformulations were evaluated for aerodynamic characteristics, cytotoxicity, hemocompatibility, macrophage phenotype analysis, and immune regulation. Cellular uptake imaging was also conducted to evaluate the uptake of NPs. The nanopowders did not pose any significant toxicity to the cells, along with good compatibility with red blood cells (RBCs). The pro-inflammatory costimulatory markers were upregulated, demonstrating the activation of T-cell response. Moreover, the NPs did not show any tolerogenic effect on the macrophages. Furthermore, confocal imaging exhibited the translocation of NPs in the cells. Altogether, the findings present that nano-DPI was found to be a promising vehicle for targeting macrophages.

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects

“…During hemostasis, CS can induce the aggregation of platelets and plasma proteins to help the blood clotting and vasoconstriction at the injured site [ 64 , 65 , 66 , 67 ]. Moreover, CS has been found to enhance the function of polymorphonuclear leukocytes, macrophages, and fibroblasts [ 68 ]. In a study, CS was found to promote the production of hyaluronic acid at the injury site, which induced wound healing faster [ 69 ].…”

A Current Perspective on the Potential of Nanomedicine for Anti-Tuberculosis Therapy

“…The drug delivery to intracellular Mtb in macrophages can be targeted by altering the physicochemical and surface characteristics of nanoparticles and by adapting a hybrid nano-approach, i.e., by using polymers that act as ligands and target specific receptors [ 43 ]. Mukhtar M et al demonstrated the promising anti-TB activity of mannosylated-chitosan and hyaolorunic-acid nanoparticles containing isoniazid, which targeted the CD44 and mannose receptors of macrophages [ 55 ]. The novel MmpL3 (mycobacterial membrane protein large 3) inhibitors, BM625 and BM819, in nanoemulsion and niosomes, showed potent antimycobacterial activity against Mtb [ 56 ].…”

Innovative Therapeutic Approaches Based on Nanotechnology for the Treatment and Management of Tuberculosis

“…The research indicate that the mannosylated models are an effective and safe approach to treating tuberculosis. 216 Mannosylated chitosan nanoparticles conjugated hyaluronic acid (HA) that loaded with isoniazid were synthesized by Mukhtar et al in 2022 and successfully used as an inhalation powder for the treatment of TB. 217…”