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用膜上皮细胞优化一种体外方法,以评估吸入药物的肺透性

Nitesh Shirsath¹, Rohit Chaudhari¹, Avinash More¹

¹Discovery Biology Division, Cipla Ltd., Vikhroli, Mumbai 400083, India.

Journal of pharmacological and toxicological methods

|June 9, 2024

概括

一个使用膜细胞的新体外模型有效地测量吸入器中的药物吸收. 该模型有助于开发更好的吸入药物治疗肺部疾病,改善药物输送和配方选择.

科学领域:

药物通过肺部输送.
在体外建模模型.
药理动力学药理动力学

背景情况:

吸入药物输送对于治疗肺部疾病至关重要,因为肺部的表面积很大.
压力计量剂量吸入器 (pMDIs) 是用于肺部药物输送的常见设备.
建立可靠的模型来研究肺部药物吸收是必不可少的.

研究的目的:

建立一个全面的体外模型来评估药物穿透度穿过膜上皮屏障.
使用II型膜上皮细胞和贝克罗梅他二 (BDP) 作为模型系统.
用 pMDI 输送系统来评估药物吸收率.

主要方法:

标准化II型膜上皮细胞培养条件 (密度,活力,化,完整性).
使用经过修改的双阶段冲击器 (TSI) 与细胞培养插件用于药物输送和沉积从pMDI.
验证的生物分析方法用于同时量化BDP及其代谢物 (17-BMP).
确定明显的透性,以评估药物吸收程度和速度.

主要成果:

优化细胞培养条件:0.55 × 10^5细胞/厘米^2在空气液体接口下8-12天.
药物透 (BDP和17-BMP) 和时间之间证明了线性相关性.
观察到的比例透性概况,表明药物吸收的一致性.

结论:

开发了一种强大的体外模型,用于研究穿过膜层的药物运输.
这个模型在药物配方开发中为药物比较研究提供了显著的价值.
促进了对肺部疾病有前途的临床候选人的选择.

关键词:

吸收方式吸收方式在BCS中,BCS是指BCS.吸入式吸入方式透性透性的第二种类型的膜细胞.

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