Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

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dc.contributor.authorMotiei, Marjancs
dc.contributor.authorMišík, Ondrejcs
dc.contributor.authorThanh Huong, Truongcs
dc.contributor.authorLízal, Františekcs
dc.contributor.authorHumpolíček, Petrcs
dc.contributor.authorSedlařík, Vladimírcs
dc.contributor.authorSáha, Petrcs
dc.coverage.issue1cs
dc.coverage.volume18cs
dc.date.issued2023-03-10cs
dc.description.abstractIn this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4.en
dc.formattextcs
dc.format.extent1-16cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationDiscover nano. 2023, vol. 18, issue 1, p. 1-16.en
dc.identifier.doi10.1186/s11671-023-03781-0cs
dc.identifier.issn2731-9229cs
dc.identifier.orcid0000-0003-4683-5145cs
dc.identifier.orcid0000-0002-0389-608Xcs
dc.identifier.other184894cs
dc.identifier.researcheridD-4363-2018cs
dc.identifier.scopus54966786300cs
dc.identifier.urihttp://hdl.handle.net/11012/244720
dc.language.isoencs
dc.publisherSpringer Naturecs
dc.relation.ispartofDiscover nanocs
dc.relation.urihttps://link.springer.com/article/10.1186/s11671-023-03781-0cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2731-9229/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectNano-in-microparticlesen
dc.subjectPulmonary deliveryen
dc.subjectChitosanen
dc.subjectSmall moleculesen
dc.subjectmiRNAsen
dc.titleEngineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAsen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-184894en
sync.item.dbtypeVAVen
sync.item.insts2025.02.03 15:47:16en
sync.item.modts2025.01.17 16:48:49en
thesis.grantorVysoké učení technické v Brně. Fakulta strojního inženýrství. EÚ-odbor termomechaniky a techniky prostředícs
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