Evora C, Soriano I, Rogers R A, Shakesheff K N, Hanes J, Langer R
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
J Control Release. 1998 Feb 12;51(2-3):143-52. doi: 10.1016/s0168-3659(97)00149-1.
This study examines the potential of 1,2-dipalmitoylphosphatidylcholine (DPPC), a major component of lung surfactant, to reduce the phagocytosis of microspheres by altering the cellular interactions occurring in the alveoli. These microspheres could be designed to act as a controlled delivery system for small molecules, peptides or proteins for pulmonary administration. Microspheres were prepared using poly (lactic-co-glycolic acid) (PLGA, 50/50 and encapsulated peroxidase as a model protein. DPPC was included in some formulations. The interaction of PLGA and DPPC-PLGA microspheres with phagocytic cells was evaluated using lung macrophages in culture. X-ray Photoelectron Spectra (XPS) results indicate that the inclusion of DPPC in the microspheres alters the microsphere surface chemistry, with the DPPC covering a large portion of the microsphere surface. The dominance of DPPC on the microsphere surface is highly beneficial in moderating the interaction occurring between the microspheres and phagocytic cells in the lung. Fluorescent confocal microscopy indicates that only 25% of cells internalized DPPC-coated particles, whereas 70% of those cells exposed to particles without the DPPC coating internalized particles after one hour of incubation.
本研究考察了肺表面活性剂的主要成分1,2-二棕榈酰磷脂酰胆碱（DPPC）通过改变肺泡中发生的细胞相互作用来减少微球吞噬作用的潜力。这些微球可设计用作小分子、肽或蛋白质肺部给药的控释系统。使用聚（乳酸-乙醇酸）共聚物（PLGA，50/50）制备微球，并将过氧化物酶作为模型蛋白进行包封。部分制剂中包含DPPC。使用培养的肺巨噬细胞评估PLGA和DPPC-PLGA微球与吞噬细胞的相互作用。X射线光电子能谱（XPS）结果表明，微球中加入DPPC会改变微球表面化学性质，DPPC覆盖了微球表面的大部分区域。DPPC在微球表面占主导地位，对调节肺中微球与吞噬细胞之间的相互作用非常有利。荧光共聚焦显微镜显示，仅25%的细胞内化了DPPC包被的颗粒，而在孵育1小时后，70%暴露于无DPPC包被颗粒的细胞内化了颗粒。
