Ickenstein Ludger M, Sandström Maria C, Mayer Lawrence D, Edwards Katarina
Faculty of Pharmaceutical Sciences, University of British Columbia, and Department of Advanced Therapeutics, The British Columbia Cancer Agency Research Centre, 601 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.
Biochim Biophys Acta. 2006 Feb;1758(2):171-80. doi: 10.1016/j.bbamem.2006.02.016. Epub 2006 Mar 10.
Upon storage of phospholipid liposome samples, lysolipids, fatty acids, and glycerol-3-phosphatidylcholine are generated as a result of acid- or base-catalyzed hydrolysis. Accumulation of hydrolysis products in the liposome membrane can induce fusion, leakage, and structural transformations of the liposomes, which may be detrimental or beneficial to their performance depending on their applications as, e.g., drug delivery devices. We investigated in the present study the influence of phospholipid hydrolysis on the aggregate morphology of DPPC/DSPE-PEG2000 liposomes after transition of the phospholipid membrane from the gel phase to liquid crystalline phase using high performance liquid chromatography (HPLC) in combination with static light scattering, dynamic light scattering, and cryo-transmission electron microscopy (cryo-TEM). The rates of DPPC hydrolysis in DPPC/DSPE-PEG2000 liposomes were investigated at a pH of 2, 4, or 6.5 and temperatures of 22 degrees C or 4 degrees C. Results indicate that following phase transition, severe structural reorganizations occurred in liposome samples that were partially hydrolyzed in the gel phase. The most prominent effect was an increasing tendency of liposomes to disintegrate into membrane discs in accordance with an increasing degree of phospholipid hydrolysis. Complete disintegration occurred when DPPC concentrations had decreased by, in some cases, as little as 3.6%. After extensive phospholipid hydrolysis, liposomes and discs fused to form large bilayer sheets as well as other more complex bilayer structures apparently due to a decreased ratio of lysolipid to palmitic acid levels in the liposome membrane.
在磷脂脂质体样品储存过程中，由于酸或碱催化的水解作用，会生成溶血磷脂、脂肪酸和甘油 - 3 - 磷脂酰胆碱。水解产物在脂质体膜中的积累可诱导脂质体的融合、渗漏和结构转变，根据其作为药物递送装置等应用，这些变化可能对其性能有害或有益。在本研究中，我们使用高效液相色谱（HPLC）结合静态光散射、动态光散射和冷冻透射电子显微镜（cryo - TEM），研究了磷脂水解对DPPC/DSPE - PEG2000脂质体磷脂膜从凝胶相转变为液晶相后的聚集体形态的影响。在pH值为2、4或6.5以及温度为22℃或4℃的条件下，研究了DPPC/DSPE - PEG2000脂质体中DPPC的水解速率。结果表明，相变后，在凝胶相中部分水解的脂质体样品发生了严重的结构重组。最显著的影响是，随着磷脂水解程度的增加，脂质体分解成膜盘的趋势增强。在某些情况下，当DPPC浓度仅降低3.6%时就会发生完全分解。大量磷脂水解后，脂质体和膜盘融合形成大的双层片以及其他更复杂的双层结构，这显然是由于脂质体膜中溶血磷脂与棕榈酸水平的比例降低所致。
