School of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette, Indiana 47907-2100, USA.
Langmuir. 2010 May 18;26(10):6932-42. doi: 10.1021/la904183e.
Dispersions of dipalmitoylphosphatidylcholine (DPPC) vesicles at 0.1 wt % (1000 ppm) in aqueous isotonic buffer solutions produced by extensive sonication were found to be colloidally stable for hours and days. They also had very low (<10 mN/m) dynamic surface tension minima (DSTM) under pulsating area conditions at 37 degrees C at 20 rpm area pulsation rate. When a 1000 ppm DPPC dispersion was mixed with a stable solution of 1000 ppm bovine serum albumin (BSA), it became colloidally unstable, aggregating within minutes, implying that heterocoagulation between lipid vesicles and albumin takes place. The heterocoagulated dispersion produced high DSTM because the lipid transport rate to the interface became slower. Moreover, the protein may have been transported to the surface faster and adsorbed more than the lipid at the surface. DPPC lipid vesicles were modified for reducing aggregation with other vesicles or with the protein with the addition of a small weight fraction of a neutral "PEGylated" lipid, with a covalently bonded poly(ethylene glycol) (PEG) group. The mixed vesicles were found to be quite more stable than the DPPC vesicles, remaining stable for months, apparently stabilized by steric forces. The colloidal stability at the initial stages of coagulation was evaluated quantitatively from the Fuchs-Smoluchowski stability ratio W. When the modified lipid vesicle dispersion was mixed with the albumin, the vesicles showed no tendency to aggregate with the albumin molecules for days, also probably because of steric repulsion between the PEGylated lipid and the protein. Finally, the mixed lipid dispersions maintained their low DSTM as did the DPPC vesicles without the albumin, and also in the presence of albumin. The results have implications on the use of DPPC or DPPC-based lipids in treating alveolar respiratory diseases without albumin inhibition of their surface tension lowering ability.
经充分超声处理后，在水合等渗缓冲溶液中浓度为 0.1wt%（1000ppm）的二棕榈酰磷脂酰胆碱（DPPC）囊泡在数小时和数天内保持胶体稳定。在 37°C 时以 20rpm 的交变面积率进行脉动面积条件下，它们的动态表面张力最小值（DSTM）也非常低（<10mN/m）。当 1000ppm DPPC 分散体与 1000ppm 牛血清白蛋白（BSA）的稳定溶液混合时，它变得胶体不稳定，在数分钟内聚集，这意味着脂质囊泡和白蛋白之间发生异凝聚。由于脂质向界面的传递速率变慢，异凝聚分散体产生了较高的 DSTM。此外，与脂质相比，蛋白质可能更快地被运送到表面并在表面上吸附更多。通过添加少量中性“PEGylated”脂质，用共价键合的聚（乙二醇）（PEG）基团对 DPPC 脂质囊泡进行改性，以减少与其他囊泡或与蛋白质的聚集。混合囊泡比 DPPC 囊泡更稳定，在数月内保持稳定，显然是由空间位阻稳定的。从福克-斯莫卢霍夫斯基稳定性比 W 定量评估胶凝初始阶段的胶体稳定性。当改性脂质囊泡分散体与白蛋白混合时，囊泡数天内没有与白蛋白分子聚集的趋势，这可能也是由于 PEGylated 脂质和蛋白质之间的空间排斥作用。最后，混合脂质分散体保持其低 DSTM，与不含白蛋白的 DPPC 囊泡相同，也存在白蛋白的情况下。这些结果对于在不抑制白蛋白降低表面张力能力的情况下使用 DPPC 或基于 DPPC 的脂质治疗肺泡呼吸疾病具有重要意义。
