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Inhalable N-acetylcysteine-loaded lactose-coated PLGA nanoparticles for tuberculosis treatment

datacite.subject.fosCiências Médicas::Ciências da Saúde
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorChaudhary, Kabi Raj
dc.contributor.authorViegas, Cláudia
dc.contributor.authorPirela, Paola
dc.contributor.authorAtalaia, Mariana
dc.contributor.authorRuivinho, Beatriz
dc.contributor.authorArora, Sanchit
dc.contributor.authorSingh, Arti
dc.contributor.authorBrandão, Pedro
dc.contributor.authorSingh, Charan
dc.contributor.authorFonte, Pedro
dc.date.accessioned2026-05-12T14:31:41Z
dc.date.available2026-05-12T14:31:41Z
dc.date.issued2025-07
dc.description.abstractObjective: Glutathione (GSH), known for having mucolytic, anti-inflammatory, and antioxidant activities, is used in clinical practice in several pathologies, including tuberculosis (TB). N-acetylcysteine (NAC) has been primarily used to treat lung conditions and paracetamol-induced liver toxicity. 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. Methods: 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 in vitro release and lung deposition studies were assessed. Results: 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 ± 3 nm, PdI of 0.15 ± 0.01, and of -11.5 ± 0.4 mV. The in vitro release study suggested a biphasic release profile. Likewise, in vitro lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, in vitro studies for antimycobacterial activity exhibited superior antibacterial activity against Mycobacterium Tuberculosis (MTB) H37Rv. Conclusions: 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.eng
dc.identifier.citationChaudhary, K.R., Viegas, C., Pirela, P. et al. Inhalable N-Acetylcysteine-loaded Lactose-coated PLGA Nanoparticles for Tuberculosis Treatment. Pharm Res 42, 1153–1165 (2025). https://doi.org/10.1007/s11095-025-03889-1
dc.identifier.doi10.1007/s11095-025-03889-1
dc.identifier.issn1573-904X
dc.identifier.urihttp://hdl.handle.net/10400.26/63080
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Nature
dc.relation.hasversionhttps://doi.org/10.1007/s11095-025-03889-1
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectdry powder
dc.subjectinhalable particles
dc.subjectN-acetylcysteine
dc.subjectPLGA nanoparticles
dc.subjectpulmonary delivery
dc.subjecttuberculosis
dc.titleInhalable N-acetylcysteine-loaded lactose-coated PLGA nanoparticles for tuberculosis treatmenteng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.endPage1165
oaire.citation.startPage1153
oaire.citation.titlePharmaceutical Research
oaire.citation.volume42
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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