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Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment.
García-Fernández, Alba; Sancho, Mónica; Bisbal, Viviana; Amorós, Pedro; Marcos, María D; Orzáez, Mar; Sancenón, Félix; Martínez-Máñez, Ramón.
  • García-Fernández A; Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain; Unidad Mixta UPV-CIPF de Investigación en Mecanismos
  • Sancho M; Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Valencia, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, València, Spain; Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, Valencia 46012, Spain.
  • Bisbal V; Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, Valencia 46012, Spain.
  • Amorós P; Instituto Universitario de Ciencia de los Materiales (ICMUV), Universitat de València, Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
  • Marcos MD; Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Spain; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, Valencia 46022, Spain; CIBER de Bioingenier
  • Orzáez M; Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Valencia, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, València, Spain; Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, Valencia 46012, Spain.
  • Sancenón F; Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Spain; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, Valencia 46022, Spain; CIBER de Bioingenier
  • Martínez-Máñez R; Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Spain; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, Valencia 46022, Spain; CIBER de Bioingenier
J Control Release ; 337: 14-26, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1306406
ABSTRACT
Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1ß cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1ß levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / Acute Lung Injury Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / Acute Lung Injury Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2021 Document Type: Article