Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität , Giessen 35392, Germany.
Institut Galien, Faculté de Pharmacie, Université Paris-Sud XI , Châtenay-Malabry 92290, France.
Langmuir. 2018 Jan 9;34(1):540-545. doi: 10.1021/acs.langmuir.7b03818. Epub 2017 Dec 19.
To minimize an unwanted interference of colloidal drug delivery vehicles with the biophysical functionality of lung surfactant, the surface of polymer nanoparticles was modified with poly(ethylene glycol) (PEGylation). Plain poly(lactide) nanoparticles provoked a statistically relevant decrease in the surface activity of the naturally derived lung surfactant, Alveofact. By contrast, the extent of lung surfactant inhibition induced by PEGylated polymer nanoparticles was significantly attenuated. Here, escalations of the PEG coating layer thickness (>3 nm, with a chain-to-chain distance of ≤4 nm) on the colloidal surface were capable of circumventing bioadverse effects. Accordingly, polymer nanoparticles equipped with PEG chains with a molecular weight above 2-5 kDa were compatible with the biophysical function of Alveofact. Overall, PEGylation of polymer nanoparticles presents a promising approach for the development of inhalation nanomedicines revealing negligible effects on the surface activity of the lining layer present in the deep lungs.
为了将胶体药物传递载体最小化地干扰肺表面活性剂的生物物理功能，聚合物纳米粒子的表面用聚乙二醇（PEGylation）进行了修饰。普通的聚乳酸纳米粒子会引起天然来源的肺表面活性剂 Alveofact 的表面活性出现统计学上的显著下降。相比之下，PEG 化聚合物纳米粒子引起的肺表面活性剂抑制的程度显著减弱。在这里，胶体表面上的 PEG 涂层厚度增加（>3nm，链间距离≤4nm）可以避免生物不良反应。因此，带有分子量大于 2-5kDa 的 PEG 链的聚合物纳米粒子与 Alveofact 的生物物理功能兼容。总的来说，聚合物纳米粒子的 PEG 化是开发吸入式纳米药物的一种很有前途的方法，对深层肺部衬里层的表面活性几乎没有影响。
