Department of Clinical Biochemistry, Ben-Gurion University, Beer Sheva, Israel.
J Liposome Res. 2010 Jun;20(2):147-59. doi: 10.3109/08982100903218900.
Effective targeted drug delivery by cationic liposomes is difficult to achieve because of their rapid clearance from the blood circulation. Bolaamphiphiles that form monolayer membrane may provide vesicles with improved stability, as shown for archaeosomes. We investigated a series of bolaamphiphiles with acetylcholine head groups and systematic structural changes in their hydrophobic domain for their ability to form stable nanovesicles. Bolaamphiphiles with two aliphatic chains separated by a short amide midsection produced spherical nanovesicles ranging in diameter from 80 to 120 nm. These vesicles lost their encapsulated material within 24 hours of incubation in phosphate-buffered saline (PBS). Similar bolaamphiphiles with a longer midsection produced a mixture of fibers and more stable nanovesicles. Bolaamphiphiles with ester amide midsection produced only spherical nanovesicles that were stable during incubation in PBS for several days. Vesicles made from bolaamphiphiles with acetylcholine head groups conjugated to the aliphatic chain via the amine were less stable than vesicles made from bolaamphiphiles with head groups conjugated to the aliphatic chain via the acetyl group. Vesicles that were stable in vitro showed good stability in the blood circulation after intravenous administration to mice. These results help in elucidating the bolaamphiphile structures needed to form stable cationic vesicles for targeted drug delivery.
阳离子脂质体的有效靶向药物递送难以实现，因为它们会从血液循环中迅速清除。形成单层膜的双性嵌段分子可能会提高囊泡的稳定性，正如在类病毒体中所显示的那样。我们研究了一系列具有乙酰胆碱头基的双性嵌段分子，并对其疏水区进行了系统的结构改变，以考察它们形成稳定的纳米囊泡的能力。具有两条脂肪链且由酰胺中间部分隔开的双性嵌段分子可生成直径为 80 至 120nm 的球形纳米囊泡。这些囊泡在磷酸盐缓冲盐水（PBS）中孵育 24 小时内会失去包封的物质。具有较长中间部分的类似双性嵌段分子则会生成纤维和更稳定的纳米囊泡的混合物。具有酯酰胺中间部分的双性嵌段分子仅生成稳定的球形纳米囊泡，在 PBS 中孵育数天也不会发生变化。通过胺键将乙酰胆碱头基连接到脂肪链上的双性嵌段分子形成的囊泡不如通过乙酰基连接到头基上的双性嵌段分子形成的囊泡稳定。在体外稳定的囊泡在静脉注射到小鼠体内后的血液循环中显示出良好的稳定性。这些结果有助于阐明形成稳定的阳离子囊泡以用于靶向药物递送所需的双性嵌段分子结构。
