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

datacite.subject.sdg03:Saúde de Qualidade
datacite.subject.sdg09:Indústria, Inovação e Infraestruturas
datacite.subject.sdg04:Educação de Qualidade
dc.contributor.authorChaudhary, Kabi Raj
dc.contributor.authorMestre Viegas, Cláudia Sofia
dc.contributor.authorPirela, Paola
dc.contributor.authorAtalaia, Mariana
dc.contributor.authorRuivinho, Beatriz Lourenço
dc.contributor.authorArora, Sanchit
dc.contributor.authorSingh, Arti
dc.contributor.authorBrandão, Pedro
dc.contributor.authorSingh, Charan
dc.contributor.authorFonte, Pedro
dc.date.accessioned2026-04-09T10:00:45Z
dc.date.available2026-04-09T10:00:45Z
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.doi10.1007/s11095-025-03889-1
dc.identifier.eissn1573-904X
dc.identifier.issn0724-8741
dc.identifier.urihttp://hdl.handle.net/10400.1/28625
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Science and Business Media LLC
dc.relationAlgarve Centre for Marine Sciences
dc.relationAlgarve Centre for Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.relationInstitute for Bioengineering and Biosciences
dc.relationInstitute for Bioengineering and Biosciences
dc.relationInstitute for Health and Bioeconomy
dc.relationEgas Moniz Interdisciplinary Research Center
dc.relation.ispartofPharmaceutical Research
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.typejournal article
dspace.entity.typePublication
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oaire.awardNumberUIDP/04565/2020
oaire.awardNumberLA/P/0140/2020
oaire.awardNumberUIDB/04585/2020
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleCentre for Marine and Environmental Research
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardTitleInstitute for Health and Bioeconomy
oaire.awardTitleEgas Moniz Interdisciplinary Research Center
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
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oaire.citation.endPage1165
oaire.citation.issue7
oaire.citation.startPage1153
oaire.citation.titlePharmaceutical Research
oaire.citation.volume42
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oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameMestre Viegas
person.familyNameRuivinho
person.familyNameFonte
person.givenNameCláudia Sofia
person.givenNameBeatriz Lourenço
person.givenNamePedro
person.identifier.ciencia-idBC13-CBFD-ECA6
person.identifier.ciencia-id2410-123D-3385
person.identifier.orcid0000-0001-6668-2778
person.identifier.orcid0009-0002-7615-8122
person.identifier.orcid0000-0002-1115-9282
person.identifier.ridK-3215-2013
person.identifier.scopus-author-id55146900200
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