2026-06-27T15:27:01Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/77092023-08-27T18:02:36Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Hidalgo Román, Alberto author García-Mouton, Cristina author Autilio, Chiara author Carravilla, Pablo author Orellana Moraleda, Guillermo author Islam, Mohammad N. author Bhattacharya, Jahar author Bhattacharya, Sunita author Cruz Rodríguez, Antonio author Pérez-Gil, Jesús 2023-06-17T08:57:32Z 2023-06-17T08:57:32Z 2020-11-24 0168-3659; Electronic: 1873-4995 10.1016/j.jconrel.2020.11.042 https://hdl.handle.net/20.500.14352/7709 https://doi.org/10.1016/j.jconrel.2020.11.042 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. eng Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations journal article URL https://docta.ucm.es/bitstreams/5577b38a-4532-469b-83e0-14f720665e1f/download File MD5 ef19eabc2db332958f3217293b861415 12663220 application/pdf Hidalgo, Alberto et al. 2020. Pulmonary surfactant and drug...pdf