RT Journal Article
T1 Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations
A1 Hidalgo Román, Alberto
A1 García-Mouton, Cristina
A1 Autilio, Chiara
A1 Carravilla, Pablo
A1 Orellana Moraleda, Guillermo
A1 Islam, Mohammad N.
A1 Bhattacharya, Jahar
A1 Bhattacharya, Sunita
A1 Cruz Rodríguez, Antonio
A1 Pérez-Gil, Jesús
AB 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.
PB Elsevier
SN 0168-3659; Electronic: 1873-4995
YR 2020
FD 2020-11-24
LK https://hdl.handle.net/20.500.14352/7709
UL https://hdl.handle.net/20.500.14352/7709
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Gobierno Vasco
NO Universidad del País Vasco
NO US National Institutes of Health
DS Docta Complutense
RD 17 abr 2025