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Título: | Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations |
Autor: | Hidalgo, Alberto; García-Mouton, Cristina; Autilio, Chiara; Carravilla, Pablo CSIC ORCID; Orellana, Guillermo; Islam, Mohammad N.; Bhattacharya, Jahar; Bhattacharya, Sunita; Cruz, Antonio; Pérez-Gil, Jesús | Palabras clave: | Air-liquid interfaces Airways Drug delivery Interfacial delivery Pulmonary surfactant Respiratory surface |
Fecha de publicación: | 10-ene-2021 | Editor: | Elsevier BV | Citación: | Journal of Controlled Release 329: 205-222 (2021) | Resumen: | 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 anti-inflammatory 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. | Versión del editor: | https://doi.org/10.1016/j.jconrel.2020.11.042 | URI: | http://hdl.handle.net/10261/314207 | DOI: | 10.1016/j.jconrel.2020.11.042 | ISSN: | 0168-3659 | E-ISSN: | 1873-4995 |
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