Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Munich, Germany.
QRSKIN GmbH, Friedrich-Bergius-Ring 15, Würzburg, Germany.
J Pharm Sci. 2021 Aug;110(8):2873-2893. doi: 10.1016/j.xphs.2021.04.018. Epub 2021 Apr 30.
The widespread application of therapeutic cells requires a successful stabilization of cells for the duration of transport and storage. Cryopreservation is currently considered the gold standard for the storage of active cells; however, (freeze-) drying cells could enable higher shelf life stability at ambient temperatures and facilitate easier transport and storage. During (freeze-) drying, freezing, (primary and secondary) drying and also the reconstitution step pose the risk of potential cell damage. To prevent these damaging processes, a wide range of protecting excipients has emerged, which can be classified, according to their chemical affiliation, into sugars, macromolecules, polyols, antioxidants and chelating agents. As many excipients cannot easily permeate the cell membrane, researchers have established various techniques to introduce especially trehalose intracellularly, prior to drying. This review aims to summarize the main damaging mechanisms during (freeze-) drying and to introduce the most common excipients with further details on their stabilizing properties and process approaches for the intracellular loading of excipients. Additionally, we would like to briefly explain recently discovered advantages of drying microorganisms, sperm, platelets, red blood cells, and eukaryotic cells, paying particular attention to the drying technique and residual moisture content.
治疗细胞的广泛应用需要在运输和储存过程中成功稳定细胞。冷冻保存目前被认为是活性细胞储存的金标准；然而，（冷冻）干燥细胞可以实现更高的室温下储存稳定性，并更便于运输和储存。在（冷冻）干燥过程中，冷冻、（初级和次级）干燥以及再水合步骤都存在潜在细胞损伤的风险。为了防止这些破坏性过程，出现了大量的保护赋形剂，根据其化学性质，可以将其分为糖、大分子、多元醇、抗氧化剂和螯合剂。由于许多赋形剂不易穿透细胞膜，研究人员已经建立了各种技术，在干燥之前将海藻糖等物质特别引入细胞内。本综述旨在总结（冷冻）干燥过程中的主要损伤机制，并介绍最常见的赋形剂，进一步详细介绍其稳定特性以及赋形剂细胞内加载的方法。此外，我们还将简要介绍最近发现的干燥微生物、精子、血小板、红细胞和真核细胞的优势，特别关注干燥技术和残余水分含量。
