Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations.
Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations.
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DOI：
10.1016/j.jconrel.2020.11.042
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发表时间：
2021-01-10
期刊：
影响因子：
--
通讯作者：
Pérez-Gil J
中科院分区：
文献类型：
--
作者：
Hidalgo A;Garcia-Mouton C;Autilio C;Carravilla P;Orellana G;Islam MN;Bhattacharya J;Bhattacharya S;Cruz A;Pérez-Gil J
这项工作探讨了肺表面活性剂（PS）在呼吸气液界面上的药物输送策略的潜力：界面输送。使用天然纯化的猪 PS 与疏水性抗炎药物他克莫司 (TAC)（一种钙调神经磷酸酶抑制剂）相结合，在体外和体内测定了 PS 和界面辅助药物载体化的功效。体外测定是在一种新颖的双表面平衡装置中进行的，该装置旨在模拟应用于界面连接的药物供体和受体室的压缩-膨胀动力学。在此设置中，PS 通过空气-液体界面有效地运输 TAC，并具有类似压缩/膨胀呼吸的动力学，增强了快速界面辅助扩散和药物释放。 PS 辅助 TAC 车辆化的功效也在脂多糖 (LPS) 诱导的急性肺损伤 (ALI) 小鼠模型中进行了体内评估。在麻醉小鼠中，在注射给药之前，将 TAC 与 PS 联合鼻内 (i.n) 滴注。脂多糖。与单独的 TAC 预处理相比，PS/TAC 预处理导致更多的 TAC 内化到更多从支气管肺泡灌洗 (BAL) 获得的肺细胞中。此外，PS/TAC 组合（而非单独的 TAC 或 PS）减弱了 LPS 诱导的促炎作用，减少了 BAL 液中的细胞和蛋白质。这些发现表明，PS 介导的 TAC 摄取增加减弱了 LPS 的促损伤作用，表明 PS/药物制剂具有协同抗炎作用。这些体外和体内结果证实了 PS 的潜在用途，可以为吸入药物开辟新颖的有效递送策略。
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.
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影响因子：
3.7
作者：
Dani, Carlo;Corsini, Iuri;Buonocore, Giuseppe
通讯作者：
Buonocore, Giuseppe
影响因子：
8.9
作者：
Hachem, Ramsey R.;Yusen, Roger D.;Trulock, Elbert P.
通讯作者：
Trulock, Elbert P.
DOI：
10.1002/jbm.b.31608
发表时间：
2010-07-01
影响因子：
3.4
作者：
Chimote, G.;Banerjee, R.
通讯作者：
Banerjee, R.
DOI：
10.1016/0005-2760(89)90072-6
发表时间：
1989-03-14
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
EGBERTS, J;SLOOT, H;MAZURE, A
通讯作者：
MAZURE, A
影响因子：
3.9
作者：
Hidalgo, Alberto;Salomone, Fabrizio;Perez-Gil, Jesus
通讯作者：
Perez-Gil, Jesus