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However, NAC exhibits potential antimycobacterial activity through several mechanisms including immunomodulation, enhancement of GSH levels, and direct antimycobacterial effect. In this work, we aim to develop an effective drug delivery system for NAC for inhalable formulations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Herein, we report the development of lactose-coated NAC-loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NAC-PLGA NPs) obtained by double emulsion methodology. Lactose has a double role, as a cryoprotectant agent and dispersant for inhalable formulations. The physicochemical properties of lactose-coated NAC-PLGA NPs were examined in terms of particle size, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency, and morphology. The <jats:italic>in vitro<\/jats:italic> release and lung deposition studies were assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The physicochemical characterization studies revealed the compatibility of the drug with the selected excipients. Moreover, lactose-coated NAC-PLGA NPs showed particle size of 310\u2009\u00b1\u20093 nm, PdI of 0.15\u2009\u00b1\u20090.01, and of -11.5\u2009\u00b1\u20090.4 mV. The <jats:italic>in vitro<\/jats:italic> release study suggested a biphasic release profile. Likewise, <jats:italic>in vitro<\/jats:italic> lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, <jats:italic>in vitro<\/jats:italic> studies for antimycobacterial activity exhibited superior antibacterial activity against <jats:italic>Mycobacterium Tuberculosis<\/jats:italic> (MTB) H37Rv.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These preliminary findings suggest that lactose-coated NAC-PLGA NPs can open the door to new therapeutic options against one of the most drug-refractory and drug-resistant infectious diseases, TB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11095-025-03889-1","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:27:59Z","timestamp":1752161279000},"page":"1153-1165","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhalable N-Acetylcysteine-loaded Lactose-coated PLGA Nanoparticles for Tuberculosis Treatment"],"prefix":"10.1007","volume":"42","author":[{"given":"Kabi Raj","family":"Chaudhary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udia","family":"Viegas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Pirela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Atalaia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Ruivinho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanchit","family":"Arora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arti","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Brand\u00e3o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charan","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-9282","authenticated-orcid":false,"given":"Pedro","family":"Fonte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"3889_CR1","doi-asserted-by":"publisher","first-page":"104649","DOI":"10.1016\/j.meegid.2020.104649","volume":"87","author":"A Alam","year":"2021","unstructured":"Alam A, Imam N, Siddiqui MF, Ali MK, Ahmed MM, Ishrat R. 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