A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition
A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition
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DOI：
10.1007/s11095-017-2169-4
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发表时间：
2017-12-01
影响因子：
3.7
通讯作者：
Forbes, Ben
中科院分区：
文献类型：
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作者：
Kumar, Abhinav;Terakosolphan, Wachirun;Forbes, Ben
根据人体呼吸道内壁液的成分来表征生物相关模拟肺液 (SLF)。将 SLF 与其他用作肺液体模拟物的介质在液体结构、生物相容性和吸入生物制药测定中的性能方面进行了比较。使用低温透射电子显微镜、光子相关光谱和 Langmuir 等温线研究了 SLF 的结构。通过MTT测定、形态测量观察和转录组分析确定与A549肺泡上皮细胞的生物相容性。通过测量二丙酸倍氯米松 (BDP) 和丙酸氟替卡松 (FP) 在 SLF 中的溶解度和溶出度来评估生物制药适用性。SLF 表现出胶体结构，具有与肺液提取物中发现的性质相似的囊泡。暴露于 SLF 24 小时后，对 A549 细胞没有明显的不利影响，尽管一些代谢变化与培养基成分变为更像肺的成分一致。与 Gamble 溶液相比，BDP 和 FP 在 SLF 中的溶解度和溶出度得到增强。本文报道的 SLF 构成了一种生物相关合成模拟物，适合研究吸入药物的生物制药特性，例如为吸入生物制药分类系统提出的那些药物。
To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.