基于人体呼吸道衬液成分的生物相容性合成肺液。
A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.
机构信息
Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK.
Institute of Pharmacy,, Martin-Luther-Universität Halle-Wittenberg, 06108, Halle (Saale), Germany.
出版信息
Pharm Res. 2017 Dec;34(12):2454-2465. doi: 10.1007/s11095-017-2169-4. Epub 2017 May 30.
PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
目的
基于人呼吸道衬液的组成来描述一种生物相关的模拟肺液（SLF）。将 SLF 与其他已被用作肺液模拟物的介质进行比较，比较的方面包括液体结构、生物相容性以及在吸入生物药剂学测定中的性能。
方法
使用冷冻传输电子显微镜、光子相关光谱法和 Langmuir 等温线来研究 SLF 的结构。通过 MTT 测定法、形态计量观察和转录组分析来确定其与 A549 肺泡上皮细胞的生物相容性。通过测量倍氯米松二丙酸酯（BDP）和丙酸氟替卡松（FP）在 SLF 中的溶解度和溶解性能来评估其生物药剂学适用性。
结果
SLF 表现出胶体结构，具有类似于肺液提取物中发现的囊泡。在暴露于 SLF 24 小时后，对 A549 细胞没有明显的不良影响，尽管鉴定出一些代谢变化与培养基向更类似肺的成分的变化一致。与 Gamble 溶液相比，BDP 和 FP 在 SLF 中的溶解度和溶解性能得到增强。
结论
本文报道的 SLF 构成了一种生物相关的合成模拟物，适合研究吸入药物的生物药剂学特性，如拟用于吸入生物药剂学分类系统的药物。
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