Christian Albrecht University Kiel, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a, 24118 Kiel, Germany.
Int J Pharm. 2011 Jun 15;411(1-2):98-105. doi: 10.1016/j.ijpharm.2011.03.053. Epub 2011 Mar 29.
There are not many excipients already approved in drug products for the use in the respiratory tract. In this study, a rapid in vitro screening procedure to assess and compare acute toxicity of soluble excipient substances on respiratory epithelial cells utilising the Calu-3 cell line is presented. The test substances are either dissolved in HBSS+HEPES buffer or are directly applied to the cellular surface. After 4h incubation, the substances are removed and the cell viability is assessed using an MTT assay. The tested excipients include polysorbate 20 and 80, lactose and povidone 30 as well as glycerol and propylene glycol as examples of excipients already being used in formulations for application in the respiratory tract. These substances are sorted according to their toxic effect and new excipients not yet used in the respiratory tract like HPMC can be classified in this scheme. With this, besides information from systemic toxicity tests, a first valuation of the acute toxic effect of the substance on respiratory epithelial cells is gained. This can aid in the choice of new excipients being necessary for modern respiratory formulations comprising new active compounds as biomolecules or new delivery strategies such as sustained or prolonged delivery.
用于呼吸道的药物产品中已批准的赋形剂并不多。在这项研究中，提出了一种利用 Calu-3 细胞系评估和比较可溶性赋形剂物质对呼吸道上皮细胞急性毒性的快速体外筛选程序。测试物质要么溶解在 HBSS+HEPES 缓冲液中，要么直接施加到细胞表面。孵育 4 小时后，用 MTT 测定法评估物质的细胞活力。测试的赋形剂包括聚山梨醇酯 20 和 80、乳糖和聚维酮 30 以及甘油和丙二醇，它们是已经用于呼吸道制剂的赋形剂的示例。这些物质根据其毒性作用进行分类，像 HPMC 这样尚未用于呼吸道的新赋形剂也可以按照这种方案进行分类。通过这种方式，除了来自全身毒性测试的信息外，还可以获得该物质对呼吸道上皮细胞急性毒性的初步评估。这有助于选择新的赋形剂，这些赋形剂对于包含生物分子等新型活性化合物或持续或延长释放等新型输送策略的现代呼吸道制剂是必要的。
