Development of siRNA and Budesonide Dual-Loaded Hybrid Lipid–Polymer Nanoparticles by Microfluidics Technology as a Platform for Dual Drug Delivery to Macrophages : An In Vitro Mechanistic Study

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dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorCerdá, Sandra Lópezen_US
dc.contributor.authorFontana, Flaviaen_US
dc.contributor.authorWang, Shiqien_US
dc.contributor.authorCorreia, Alexandraen_US
dc.contributor.authorMolinaro, Giuseppinaen_US
dc.contributor.authorTello, Rubén Parejaen_US
dc.contributor.authorHirvonen, Jounien_US
dc.contributor.authorCelia, Christianen_US
dc.contributor.authorBarreto, Goncaloen_US
dc.contributor.authorSantos, Hélder A.en_US
dc.contributor.departmentDepartment of Neuroscience and Biomedical Engineeringen
dc.contributor.organizationUniversity of Helsinkien_US
dc.contributor.organizationGabriele d'Annunzio Universityen_US
dc.date.accessioned2023-09-06T06:03:51Z
dc.date.available2023-09-06T06:03:51Z
dc.date.issued2023-08en_US
dc.descriptionFunding Information: H.A.S. acknowledges financial support from the Academy of Finland (Grant No. 331151) and the UMCG Research Funds. This work received funding from the European Union's Horizon 2020 research and development programme under the Marie Skłodowska Curie grant agreement No. 955685. S.W. acknowledges the financial support from the Academy of Finland (Grant No. 331106). C.C. acknowledges financial support from Strengthening of research structures and creation of R&D “Innovation Ecosystems”, “National Recovery and Resilience Plan (NRRP)”, Mission 4, Component 2 Investment 1.5, funded from the European Union–NextGenerationEU – VITALITY, ECS00000041 (Grant No. D73C22000840006). The authors thank the Electron Microscopy Unit and Light Microscopy Unit, Institute of Biotechnology, University of Helsinki (supported by HiLIFE and Biocenter Finland) for electron microscope and confocal imaging. Publisher Copyright: © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.
dc.description.abstractMacrophages play a key role in the development of many diseases, like tissue injury, cancer, and autoimmune diseases. So far, single-drug loaded nanoparticles are developed to target macrophages. Nevertheless, macrophage dysregulation can induce multiple conditions, i.e., inflammation and fibrosis. Therefore, the simultaneous codelivery of a small molecule drug and a small interfering RNA (siRNA) for gene silencing may be beneficial to modulate macrophage dysfunction. Herein, hybrid lipid–polymer nanoparticles (LPNs) coloaded with both budesonide and enhanced green fluorescence protein siRNA (eGFP-siRNA) as model anti-inflammatory small molecule drug and siRNA, respectively, are developed by an optimized microfluidics method. Specifically, a poly(lactic-co-glycolic acid) core is coated by a lipid shell, and LPNs with size homogeneity and colloidal stability are obtained. Both payloads are loaded efficiently, and a controlled release is achieved. Additionally, LPNs are nontoxic in murine RAW 264.7 cells and human THP-1 cells and are efficiently taken up by these cells. Finally, the transfection efficiency of dual-loaded LPNs is high at low LPNs doses, thus proving the suitability of this nanosystem for gene silencing. Overall, the optimized LPNs are a suitable nanoplatform for the dual drug delivery to macrophages for the treatment of complex conditions requiring dual therapeutic approaches.en
dc.description.versionPeer revieweden
dc.format.extent16
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationCerdá, S L, Fontana, F, Wang, S, Correia, A, Molinaro, G, Tello, R P, Hirvonen, J, Celia, C, Barreto, G & Santos, H A 2023, ' Development of siRNA and Budesonide Dual-Loaded Hybrid Lipid–Polymer Nanoparticles by Microfluidics Technology as a Platform for Dual Drug Delivery to Macrophages : An In Vitro Mechanistic Study ', Advanced Therapeutics, vol. 6, no. 8, 2300048 . https://doi.org/10.1002/adtp.202300048en
dc.identifier.doi10.1002/adtp.202300048en_US
dc.identifier.issn2366-3987
dc.identifier.otherPURE UUID: e143c9e1-e34f-405e-9b34-95597e423b81en_US
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/e143c9e1-e34f-405e-9b34-95597e423b81en_US
dc.identifier.otherPURE LINK: http://www.scopus.com/inward/record.url?scp=85159936579&partnerID=8YFLogxKen_US
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/120464956/Development_of_siRNA_and_Budesonide_Dual_Loaded_Hybrid_Lipid_Polymer_Nanoparticles_by_Microfluidics_Technology_as_a_Platform_for_Dual_Drug_Delivery_to_Macrophages.pdfen_US
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/123352
dc.identifier.urnURN:NBN:fi:aalto-202309065717
dc.language.isoenen
dc.publisherWiley-VCH Verlag
dc.relation.ispartofseriesAdvanced Therapeuticsen
dc.relation.ispartofseriesVolume 6, issue 8en
dc.rightsopenAccessen
dc.subject.keyworddrug deliveryen_US
dc.subject.keywordhybrid nanoparticlesen_US
dc.subject.keywordmacrophagesen_US
dc.subject.keywordmicrofluidicsen_US
dc.subject.keywordsiRNAen_US
dc.titleDevelopment of siRNA and Budesonide Dual-Loaded Hybrid Lipid–Polymer Nanoparticles by Microfluidics Technology as a Platform for Dual Drug Delivery to Macrophages : An In Vitro Mechanistic Studyen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionpublishedVersion
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