Optimization of an in vitro method for assessing pulmonary permeability of inhaled drugs using alveolar epithelial cells

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2024-06-07 DOI:10.1016/j.vascn.2024.107526
Nitesh Shirsath , Rohit Chaudhari , Avinash More , Vinay Sonawane, Jeevan Ghosalkar, Kalpana Joshi
{"title":"Optimization of an in vitro method for assessing pulmonary permeability of inhaled drugs using alveolar epithelial cells","authors":"Nitesh Shirsath ,&nbsp;Rohit Chaudhari ,&nbsp;Avinash More ,&nbsp;Vinay Sonawane,&nbsp;Jeevan Ghosalkar,&nbsp;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. Such models would create potential value during formulation development for comparative studies and selection of clinical candidates.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"128 ","pages":"Article 107526"},"PeriodicalIF":1.3000,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological and toxicological methods","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1056871924000364","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
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.
期刊最新文献
Molecular imaging of excitability difference between alkaloids/salts (nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide) In-situ polyherbal gel as biomedicine in the management of Alzheimer's disease: Understanding ameliorative potential in Trimethyltin induced neurodegeneration Evaluation of 4 quantification methods for monitoring 16 antidepressant drugs and their metabolites in human plasma by LC-MS/MS Comparative toxicity assessment of selected nanoparticles using different experimental model organisms Evaluating the proarrhythmic risk of delayed-action compounds in serum free cell culture conditions; serum-starvation accelerates/amplifies the effect of probucol on the KCNQ1 + KCNE1 channel
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1