Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Chem Phys Lipids. 2013 Feb-Mar;167-168:1-8. doi: 10.1016/j.chemphyslip.2013.01.003. Epub 2013 Jan 14.
Liposomes required for drug delivery are commonly obtained by extrusion of phospholipid vesicle suspensions through track-etched membranes. The effects of trans-membrane pressure, membrane pore size and bilayer composition on extruded liposome size are well-studied. Vesicle suspensions used in these extrusion studies are highly polydisperse, ranging from 20 nm to 100 μm. Vesicle sub-populations smaller than membrane pore size do not undergo extrusion-mediated size reduction and contribute significantly to the mean radius of extruded liposomes. In the present work, giant unilamellar vesicles (GUVs) are isolated by subjecting electroformed vesicle suspensions to low-pressure filtration. The isolated GUVs are extruded through track-etched polycarbonate membranes with pore radii ranging from 25 to 200 nm. We show that, when vesicles larger than the membrane pore size are extruded, the minimum attainable value of mean radius of resulting liposomes is independent of initial vesicle size as well as the number of extrusion cycles. We also show that bilayer composition significantly influences the extruded liposome size. These results provide new insights into the possible mechanisms of vesicle size reduction during extrusion process.
用于药物输送的脂质体通常通过将磷脂囊泡悬浮液通过刻蚀膜的微孔挤压来获得。跨膜压力、膜孔径和双层组成对挤出脂质体大小的影响已经得到了很好的研究。这些挤压研究中使用的囊泡悬浮液高度多分散，范围从 20nm 到 100μm。小于膜孔径的囊泡亚群不会经历挤压介导的尺寸减小，并对挤出脂质体的平均半径有显著贡献。在本工作中，通过对电形成的囊泡悬浮液进行低压过滤，分离出巨大的单层囊泡（GUVs）。分离出的 GUVs 通过刻蚀聚碳酸酯膜挤出，膜孔半径范围从 25nm 到 200nm。我们表明，当大于膜孔径的囊泡被挤出时，所得脂质体平均半径的最小可达值与初始囊泡大小以及挤出循环次数无关。我们还表明，双层组成对挤出脂质体的大小有显著影响。这些结果为挤压过程中囊泡尺寸减小的可能机制提供了新的见解。
