RT Journal Article T1 Dry Powder Comprised of Isoniazid-Loaded Nanoparticles of Hyaluronic Acid in Conjugation with Mannose-Anchored Chitosan for Macrophage-Targeted Pulmonary Administration in Tuberculosis A1 Mukhtar, M A1 Csaba, Noemi Stefania A1 Robla Álvarez, Sandra A1 Varela Calviño, Rubén A1 Nagy, Attila A1 Burian, Katalin A1 Kókai, Dávid A1 Ambrus, Rita K1 Dry powder inhaler K1 Immune regulation K1 Inhalation K1 Isoniazid K1 Mannose conjugation K1 Macrophage phenotype K1 Next-generation impactor K1 Tuberculosis AB 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. PB MDPI SN 1999-4923 YR 2022 FD 2022 LK https://hdl.handle.net/10347/38967 UL https://hdl.handle.net/10347/38967 LA eng NO Mukhtar, M., Csaba, N., Robla, S., Varela-Calviño, R., Nagy, A., Burian, K., Kókai, D., & Ambrus, R. (2022). Dry Powder Comprised of Isoniazid-Loaded Nanoparticles of Hyaluronic Acid in Conjugation with Mannose-Anchored Chitosan for Macrophage-Targeted Pulmonary Administration in Tuberculosis. Pharmaceutics, 14(8), 1543. https://doi.org/10.3390/pharmaceutics14081543 NO Gedeon Richter Ltd. 2.2.1-15-2016-00007 NO TKP2021-EGA funding scheme and, Ministerio de Ciencia e Innovacion RETOS - PID2019-107500RBI00 and Competitive Reference Groups NO Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, Ref: ED431C 2021/17 DS Minerva RD 24 abr 2026