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Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations



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Hidalgo Román, Alberto and García-Mouton, Cristina and Autilio, Chiara and Carravilla, Pablo and Orellana Moraleda, Guillermo and Islam, Mohammad N. and Bhattacharya, Jahar and Bhattacharya, Sunita and Cruz Rodríguez, Antonio and Pérez-Gil, Jesús (2020) Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations. Journal of Controlled Release, 329 . pp. 205-222. ISSN 0168-3659; Electronic: 1873-4995 (Submitted)

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Official URL: 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.

Item Type:Article
Uncontrolled Keywords:Interfacial delivery; Drug delivery ;Pulmonary surfactant Airways; Respiratory surface; Air-liquid interfaces
Subjects:Medical sciences > Biology > Biochemistry
ID Code:63654
Deposited On:20 Jan 2021 10:26
Last Modified:31 May 2021 10:22

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