Jörgensen Arne Matteo, Wibel Richard, Bernkop-Schnürch Andreas
Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, Innsbruck, 6020, Austria.
Small. 2023 Apr;19(17):e2206968. doi: 10.1002/smll.202206968. Epub 2023 Jan 6.
Cationic and ionizable cationic lipids are broadly applied as auxiliary agents, but their use is associated with adverse effects. If these excipients are rapidly degraded to endogenously occurring metabolites such as amino acids and fatty acids, their toxic potential can be minimized. So far, synthesized and evaluated biodegradable cationic and ionizable cationic lipids already showed promising results in terms of functionality and safety. Within this review, an overview about the different types of such biodegradable lipids, the available building blocks, their synthesis and cleavage by endogenous enzymes is provided. Moreover, the relationship between the structure of the lipids and their toxicity is described. Their application in drug delivery systems is critically discussed and placed in context with the lead compounds used in mRNA vaccines. Moreover, their use as preservatives is reviewed, guidance for their design is provided, and an outlook on future developments is given.
阳离子脂质和可离子化阳离子脂质被广泛用作辅助剂，但其使用会带来不良影响。如果这些辅料能迅速降解为内源性代谢产物，如氨基酸和脂肪酸，其潜在毒性可降至最低。到目前为止，已合成并评估的可生物降解阳离子脂质和可离子化阳离子脂质在功能和安全性方面已显示出有前景的结果。在本综述中，提供了关于此类可生物降解脂质的不同类型、可用构建单元、其合成以及被内源性酶裂解的概述。此外，还描述了脂质结构与其毒性之间的关系。对它们在药物递送系统中的应用进行了批判性讨论，并与mRNA疫苗中使用的先导化合物相关联。此外，对它们作为防腐剂的用途进行了综述，提供了其设计指导，并对未来发展进行了展望。
