One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.

中文翻译：

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脂肪酸聚甘油酯作为肺部制剂的赋形剂的体外毒性筛选。

开发肺部制剂的主要问题之一是批准的赋形剂的利用率低。脂肪酸的聚甘油酯（PGFA）是有前途的分子，可作为赋形剂用于制剂开发和药物向肺部的输送。然而，到目前为止，尚未研究它们在深肺中的生物相容性。主要暴露的细胞包括肺泡上皮细胞和肺泡巨噬细胞。由于PGFA的水溶性差，预期肺泡巨噬细胞的暴露将比上皮细胞的暴露高得多。在这项研究中，测试了两种PGFA及其混合物对上皮细胞的细胞毒性以及巨噬细胞的细胞毒性和功能损害。通过脱氢酶活性和乳酸脱氢酶释放评估细胞毒性。溶酶体功能，磷脂蓄积，吞噬作用，一氧化氮的产生和细胞因子的释放被用来评估巨噬细胞功能。细胞毒性随着PGFA分子极性的增加而增加。在浓度高于1 mg / ml的溶酶体中，注意到吞噬作用受损，一氧化氮分泌和细胞因子释放增加。所研究的浓度高达1 mg / ml的PGFA可以认为是非关键的，并且有望用于高剂量粉末的先进肺部输送和靶向肺泡巨噬细胞的药物。并注意到细胞因子的释放增加。所研究的浓度高达1 mg / ml的PGFA可以认为是非关键的，并且有望用于高剂量粉末的先进肺部输送和靶向肺泡巨噬细胞的药物。并注意到细胞因子的释放增加。所研究的浓度高达1 mg / ml的PGFA可以认为是非关键的，并且有望用于高剂量粉末的先进肺部输送和靶向肺泡巨噬细胞的药物。