Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus

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dc.contributor.authorAguilera Correa, John Jairo
dc.contributor.authorGisbert Garzarán, Miguel
dc.contributor.authorMediero, A.
dc.contributor.authorPablo Velasco, David de
dc.contributor.authorFernández Aceñero, María Jesús
dc.contributor.authorLozano Borregón, Daniel
dc.contributor.authorEsteban, J.
dc.contributor.authorVallet Regí, María Dulce Nombre
dc.date.accessioned2023-06-22T12:28:01Z
dc.date.available2023-06-22T12:28:01Z
dc.date.issued2022-10-28
dc.descriptionCRUE-CSIC (Acuerdos Transformativos 2022) RESEARCHER ID S-2443-2016 (Miguel Gisbert Garzarán) ORCID 0000-0001-9815-0354 (Miguel Gisbert Garzarán) RESEARCH ID B-5081-2017  (Daniel Lozano Borregón) ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)
dc.description.abstractOsteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. Statement of significance In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.
dc.description.departmentDepto. de Química en Ciencias Farmacéuticas
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea. Horizonte 2020
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/75371
dc.identifier.doi10.1016/j.actbio.2022.10.039
dc.identifier.issn1742-7061
dc.identifier.officialurlhttps://doi.org/10.1016/j.actbio.2022.10.039
dc.identifier.relatedurlhttps://www.ucm.es/valletregigroup
dc.identifier.urihttps://hdl.handle.net/20.500.14352/72580
dc.journal.titleActa Biomaterialia
dc.language.isoeng
dc.publisherElsevier
dc.relation.projectIDVERDI (694160)
dc.relation.projectID“Miguel Servet” program (CP15/00053).
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu615.46
dc.subject.keywordOsteomyelitis
dc.subject.keywordBiofilm
dc.subject.keywordMethicillin-resistant Staphylococcus aureus
dc.subject.keywordMesoporous silica nanoparticles
dc.subject.keywordBone-targeting
dc.subject.keywordDrug delivery
dc.subject.ucmMateriales
dc.subject.ucmQuímica inorgánica (Farmacia)
dc.subject.unesco3312 Tecnología de Materiales
dc.titleAntibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus
dc.typejournal article
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery60f38f4e-295f-4281-ba62-1902edf6f2bf
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