Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität , Giessen D-35392, Germany.
Institut Galien, Faculté de Pharmacie, Université Paris-Sud XI , Châtenay-Malabry F-92296, France.
Mol Pharm. 2017 Oct 2;14(10):3464-3472. doi: 10.1021/acs.molpharmaceut.7b00477. Epub 2017 Aug 30.
Lung-delivered polymer nanoparticles provoked dysfunction of the essential lung surfactant system. A steric shielding of the nanoparticle surface with poloxamers could minimize the unwanted interference of polymer nanoparticles with the biophysical function of lung surfactant. The extent of poly(styrene) and poly(lactide) nanoparticle-induced lung surfactant inhibition could be related to the type and content of the applied poloxamer. Escalations of the adsorbed coating layer thickness (>3 nm) as well as concentration (brush- rather than mushroom-like conformation of poly(ethylene glycol), chain-to-chain distance of <5 nm) on the colloidal surface were capable of circumventing bioadverse effects. Accordingly, specific formulations (i.e., poloxamer 188, 338, and 407) avoided a perturbation of the microstructure and surface activity of Alveofact and a depletion of the content of surfactant-associated proteins. Poloxamer-modified polymer nanoparticles represent a promising nanomedicine platform intended for respiratory delivery revealing negligible effects on the biophysical functionality of the lining layer present in the deep lungs.
肺部递送的聚合物纳米颗粒会引起肺表面活性剂系统的功能障碍。用泊洛沙姆对纳米颗粒表面进行空间位阻屏蔽，可以最大限度地减少聚合物纳米颗粒对肺表面活性剂生物物理功能的不必要干扰。聚（苯乙烯）和聚（乳酸）纳米颗粒引起的肺表面活性剂抑制的程度可能与所应用的泊洛沙姆的类型和含量有关。在胶体表面上增加吸附涂层厚度（>3nm）和浓度（刷状而非蘑菇状的聚乙二醇构象，链间距离<5nm），可以避免生物不良反应。因此，特定的配方（即泊洛沙姆 188、338 和 407）避免了对 Alveofact 的微观结构和表面活性的干扰，也避免了表面活性剂相关蛋白含量的减少。泊洛沙姆修饰的聚合物纳米颗粒代表了一种有前途的用于呼吸递药的纳米医学平台，对深层肺部衬里层的生物物理功能几乎没有影响。
