Department of Biochemical Engineering, University College London, London, WC1H 0AH, UK.
Aston Pharmacy School, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK.
Sci Rep. 2017 Sep 21;7(1):12045. doi: 10.1038/s41598-017-11533-1.
Liposomes are lipid based bilayer vesicles that can encapsulate, deliver and release low-soluble drugs and small molecules to a specific target site in the body. They are currently exploited in several nanomedicine formulations. However, their development and application is still limited by expensive and time-consuming process development and production methods. Therefore, to exploit these systems more effectively and support the rapid translation of new liposomal nanomedicines from bench to bedside, new cost-effective and scalable production methods are needed. We present a continuous process flow system for the preparation, modification and purification of liposomes which offers lab-on-chip scale production. The system was evaluated for a range of small vesicles (below 300 nm) varying in lipid composition, size and charge; it offers effective and rapid nanomedicine purification with high lipid recovery (> 98%) combined with effective removal of non-entrapped drug (propofol >95% reduction of non-entrapped drug present) or protein (ovalbumin >90% reduction of OVA present) and organic solvent (ethanol >95% reduction) in less than 4 minutes. The key advantages of using this bench-top, rapid, process development tool are the flexible operating conditions, interchangeable membranes and scalable high-throughput yields, thereby offering simultaneous manufacturing and purification of nanoparticles with tailored surface attributes.
脂质体是基于脂质的双层囊泡，可以将低溶性药物和小分子包封、递送到体内的特定靶位并释放。它们目前被应用于几种纳米医学制剂中。然而，其开发和应用仍然受到昂贵且耗时的工艺开发和生产方法的限制。因此，为了更有效地利用这些系统，并支持将新型脂质体纳米药物从实验室快速转化为临床应用，需要新的具有成本效益和可扩展的生产方法。我们提出了一种用于制备、修饰和纯化脂质体的连续工艺流系统，可实现芯片实验室规模的生产。该系统对一系列具有不同脂质组成、大小和电荷的小囊泡（<300nm）进行了评估；它提供了有效的、快速的纳米药物纯化，具有高脂质回收率（>98%），同时有效去除未包封的药物（丙泊酚>95%的未包封药物减少）或蛋白质（卵清蛋白>90%的 OVA 减少）和有机溶剂（乙醇>95%的减少），整个过程不到 4 分钟。使用这种台式、快速的工艺开发工具的主要优势在于其灵活的操作条件、可互换的膜和可扩展的高通量产量，从而能够同时制造和纯化具有定制表面属性的纳米颗粒。
