{"title":"优化利用肺泡上皮细胞评估吸入药物肺渗透性的体外方法。","authors":"Nitesh Shirsath , Rohit Chaudhari , Avinash More , Vinay Sonawane, Jeevan Ghosalkar, Kalpana Joshi","doi":"10.1016/j.vascn.2024.107526","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Inhalation of drugs for the treatment of pulmonary diseases has been used since a long time. Due to lungs' larger absorptive surface area, delivery of drugs to the lungs is the method of choice for different disorders. Here we present the establishment of a comprehensive permeability model using Type II alveolar epithelial cells and Beclomethasone Dipropionate (BDP) as a model drug delivered by pressurized metered dose inhaler (pMDI).</p></div><div><h3>Methods</h3><p>Using Type II alveolar epithelial cells, the method was standardized for parameters viz., cell density, viability, incubation period and membrane integrity. The delivery and deposition of drug were using the pMDI device with a Twin Stage Impinger (TSI) modified to accommodate cell culture insert having monolayer of cells. The analytical method for simultaneous estimation of BDP and Beclomathasone-17-Monopropionate (17-BMP) was validated as per the bioanalytical guidelines. The extent and rate of absorption of BDP was determined by quantifying the amount of drug permeated and the data represented by calculating its apparent permeability.</p></div><div><h3>Results</h3><p>Type II alveolar epithelial cells cultured at 0.55 × 10<sup>5</sup> cells/cm<sup>2</sup> for 8–12 days under air-liquid interface were optimized for conducting permeability studies. The data obtained for absorptive transport showed a linear increase in the drug permeated against time for both BDP and 17-BMP along with proportional permeability profile.</p></div><div><h3>Discussion</h3><p>We have developed a robust <em>in vitro</em> model to study absorptive rate of drug transport across alveolar layer. 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引用次数: 0
摘要
简介吸入药物治疗肺部疾病由来已久。由于肺的吸收表面积较大,向肺部给药是治疗不同疾病的首选方法。在此,我们以 II 型肺泡上皮细胞和二丙酸倍氯米松(BDP)为模型药物,通过加压计量吸入器(pMDI)建立了一个综合渗透模型:方法:使用 II 型肺泡上皮细胞,对细胞密度、活力、培养期和膜完整性等参数进行了标准化。药物的递送和沉积使用的是 pMDI 装置,该装置带有一个经过改装的双级进样器 (TSI),以适应具有单层细胞的细胞培养插入物。同时估算 BDP 和倍氯米松-17-丙酸单酯(17-BMP)的分析方法按照生物分析指南进行了验证。通过量化药物渗透量来确定 BDP 的吸收程度和速度,并通过计算表观渗透性来表示数据:在空气-液体界面下,以 0.55 × 105 个细胞/平方厘米的浓度培养 II 型肺泡上皮细胞 8-12 天,进行渗透性研究。获得的吸收转运数据显示,BDP 和 17-BMP 的药物渗透量随时间呈线性增长,同时渗透率也成比例增长:讨论:我们开发了一种稳健的体外模型来研究药物通过肺泡层的吸收转运率。这种模型将在制剂开发过程中为比较研究和临床候选药物的选择带来潜在价值。
Optimization of an in vitro method for assessing pulmonary permeability of inhaled drugs using alveolar epithelial cells
Introduction
Inhalation of drugs for the treatment of pulmonary diseases has been used since a long time. Due to lungs' larger absorptive surface area, delivery of drugs to the lungs is the method of choice for different disorders. Here we present the establishment of a comprehensive permeability model using Type II alveolar epithelial cells and Beclomethasone Dipropionate (BDP) as a model drug delivered by pressurized metered dose inhaler (pMDI).
Methods
Using Type II alveolar epithelial cells, the method was standardized for parameters viz., cell density, viability, incubation period and membrane integrity. The delivery and deposition of drug were using the pMDI device with a Twin Stage Impinger (TSI) modified to accommodate cell culture insert having monolayer of cells. The analytical method for simultaneous estimation of BDP and Beclomathasone-17-Monopropionate (17-BMP) was validated as per the bioanalytical guidelines. The extent and rate of absorption of BDP was determined by quantifying the amount of drug permeated and the data represented by calculating its apparent permeability.
Results
Type II alveolar epithelial cells cultured at 0.55 × 105 cells/cm2 for 8–12 days under air-liquid interface were optimized for conducting permeability studies. The data obtained for absorptive transport showed a linear increase in the drug permeated against time for both BDP and 17-BMP along with proportional permeability profile.
Discussion
We have developed a robust in vitro model to study absorptive rate of drug transport across alveolar layer. Such models would create potential value during formulation development for comparative studies and selection of clinical candidates.
期刊介绍:
Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.