Laboratory of Pharmaceutical Technology and Biopharmacy, Nanomedicine Developments, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, 4000 Liège, Belgium; Laboratory of Drug Development, Doctoral School of Sciences and Health, University Joseph KI-ZERBO, 03 BP 7021 Ouagadougou 03, Burkina Faso.
Laboratory of Pharmaceutical Technology and Biopharmacy, Nanomedicine Developments, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, 4000 Liège, Belgium.
Int J Pharm. 2021 Mar 15;597:120271. doi: 10.1016/j.ijpharm.2021.120271. Epub 2021 Feb 4.
Liposomes are targeted drug delivery systems that are of great pharmaceutical and therapeutic interest. Parenteral route is the main way used for liposome administration. In this case, their sterility is a requirement. However, due to the particular sensitivity of liposomes and their tendency to physicochemical alterations, their sterilization remains a real challenge. Conventional sterilization methods such as heat, ethylene oxide, ultraviolet and gamma irradiations are considered as unsuitable for liposome sterilization and the recommended methods for obtaining sterility of liposomes are filtration and aseptic manufacturing. Unfortunately, these recommended methods are not without limitations. This review outlines the difficulties associated with the use of these different classical methods for obtaining liposome sterility. The effects on liposome physicochemical and biopharmaceutical characteristics as well as efficacy, toxicity and practical problems of these sterilization techniques have been discussed. The search for an alternative method being therefore necessary, the applicability of supercritical carbon dioxide (ScCO) technology, which is nowadays a promising strategy for the sterilization of sensitive products such as liposomes, is also examined. It appears from this analysis that ScCO could effectively be an interesting alternative to achieve sterility of liposomes, but for this, sterilization assays including challenge tests and optimization studies are needed.
脂质体是靶向药物传递系统，具有重要的药物和治疗学意义。脂质体给药的主要途径是肠外途径。在这种情况下，其无菌性是一个要求。然而，由于脂质体的特殊敏感性及其理化性质改变的倾向，其灭菌仍然是一个真正的挑战。热、环氧乙烷、紫外线和伽马射线等常规灭菌方法被认为不适合脂质体灭菌，获得脂质体无菌性的推荐方法是过滤和无菌生产。不幸的是，这些推荐的方法并非没有局限性。本文概述了使用这些不同的经典方法获得脂质体无菌性所面临的困难。讨论了这些灭菌技术对脂质体理化和生物制药特性以及功效、毒性和实际问题的影响。因此，需要寻找替代方法，检查超临界二氧化碳（ScCO）技术的适用性，该技术目前是一种有前途的策略，可用于灭菌对敏感产品，如脂质体。从这项分析中可以看出，ScCO 可以有效地成为实现脂质体无菌性的一个有趣的替代方法，但为此，需要进行包括挑战性试验和优化研究在内的灭菌试验。
