Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant
Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant
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DOI：
10.1021/acs.langmuir.7b01177
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发表时间：
2017-08-15
期刊：
影响因子：
3.9
通讯作者：
Perez-Gil, Jesus
中科院分区：
文献类型：
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作者：
Hidalgo, Alberto;Salomone, Fabrizio;Perez-Gil, Jesus
肺表面活性物质是维持呼吸系统气液界面稳定的重要系统。此外，肺表面活性物质已被提出作为将药物靶向至肺的有效方法。然而，很少有研究详细探讨了药物掺入表面活性剂的机制，在生理上有意义的条件下，药物的存在对界面处肺表面活性剂性能的影响，或肺表面活性剂使用气液界面将药物运载到长距离的能力。本研究的重点是肺表面活性物质的能力，界面载体皮质类固醇，如丙酸倍氯米松（BDP）或布地奈德（BUD）作为模型药物。主要目的是（a）表征皮质类固醇掺入天然和合成表面活性剂，。(b)评价皮质类固醇的存在是否影响表面活性剂功能，和（c）确定表面活性剂制剂是否能够使BDP和BUD沿着气液界面有效地扩散和分布。我们已经比较了从猪肺和两个临床表面活性剂的纯化表面活性剂的性能：Poractant阿尔法，一种天然的表面活性剂的动物来源，广泛用于治疗早产儿，CHF 5633，一种新的合成表面活性剂制剂，目前正在临床试验。天然和临床表面活性剂均自发地掺入皮质类固醇，相对于磷脂含量，其质量分数高达至少10%。药物的存在不干扰ability.to有效地吸附到空气液体界面中并形成能够达到并维持非常低的表面张力的表面活性膜（
Pulmonary surfactant is a crucial system to stabilize the respiratory air liquid interface. Furthermore, pulmonary surfactant has been proposed as an effective method for targeting drugs to the lungs. However, few studies have examined in detail the mechanisms of incorporation of drugs into surfactant, the impact of the presence of drugs on pulmonary surfactant performance at the interface under physiologically meaningful conditions, or the ability of pulmonary surfactant to use the air liquid interface to vehiculise drugs to long distances. This study focuses on the ability of pulmonary surfactant to interfacially vehiculize corticosteroids such as beclomethasone dipropionate (BDP) or Budesonide (BUD) as model drugs. The main objectives have been to (a) characterize the incorporation of corticosteroids into natural and synthetic surfactants,. (b) evaluate whether the presence of corticosteroids affects surfactant functionality, and (c) determine whether surfactant preparations enable the efficient spreading and distribution of BDP and BUD along the air liquid interface. We have compared the performance of a purified surfactant from porcine lungs and two clinical surfactants: Poractant alfa, a natural surfactant of animal origin extensively used to treat premature babies, and CHF5633, a new synthetic surfactant preparation currently under clinical trials. Both, natural and clinical surfactants spontaneously incorporated corticosteroids up to at least 10% by mass with respect to phospholipid content. The presence of the drugs did not interfere with their ability.to efficiently adsorb into air liquid interfaces and form surface active films able to reach and sustain very low surface tensions (