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Título:
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Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations
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Autores:
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Hidalgo Román, Alberto ;
García-Mouton, Cristina ;
Autilio, Chiara ;
Carravilla, Pablo ;
Orellana Moraleda, Guillermo ;
Islam, Mohammad N. ;
Bhattacharya, Jahar ;
Bhattacharya, Sunita ;
Cruz Rodríguez, Antonio ;
Pérez Gil, Jesús
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Tipo de documento:
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texto impreso
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Editorial:
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Elsevier, 2020-11-24
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Dimensiones:
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application/pdf
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Nota general:
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info:eu-repo/semantics/restrictedAccess
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Idiomas:
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Palabras clave:
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Estado = Presentado
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Materia = Ciencias Biomédicas: Biología: Bioquímica
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Tipo = Artículo
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Resumen:
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This work explores the potential for strategizing pulmonary surfactant (PS) for drug delivery over the respiratory air-liquid interface: the interfacial delivery. The efficacy of PS- and interface-assisted drug vehiculization was determined both in vitro and in vivo using a native purified porcine PS combined with the hydrophobic antiinflammatory drug Tacrolimus (TAC), a calcineurin inhibitor. In vitro assays were conducted in a novel double surface balance setup designed to emulate compression-expansion dynamics applied to interfacially connected drug donor and recipient compartments. In this setup, PS transported TAC efficiently over air-liquid interfaces, with compression/expansion breathing-like dynamics enhancing rapid interface-assisted diffusion and drug release. The efficacy of PS-assisted TAC vehiculization was also evaluated in vivo in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In anesthetized mice, TAC combined with PS was intra-nasally (i.n) instilled prior administering i.n. LPS. PS/TAC pre-treatment caused greater TAC internalization into a higher number of lung cells obtained from bronchoalveolar lavages (BAL) than TAC pre-treatment alone. Additionally, the PS/TAC combination but not TAC or PS alone attenuated the LPS-induced pro-inflammatory effects reducing cells and proteins in BAL fluid. These findings indicated that PS-mediated increase in TAC uptake blunted the pro-injurious effects of LPS, suggesting a synergistic anti-inflammatory effect of PS/drug formulations. These in vitro and in vivo results establish the potential utility of PS to open novel effective delivery strategies for inhaled drugs.
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En línea:
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https://eprints.ucm.es/id/eprint/63654/2/Hidalgo%2C%20Alberto%20et%20al.%202020.%20Pulmonary%20surfactant%20and%20drug...pdf
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