A mechanism-based computational tool to optimize pulmonary drug delivery

一种基于机制的计算工具来优化肺部药物输送

基本信息

批准号：
9140317
负责人：
Andrzej J Przekwas
金额：
$ 47.37万
依托单位：
CFD RESEARCH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9140317
关键词：
Academia Accounting Aerosols Affect Air Allergens Asthma Biological Biological Factors Biological Products Blood Breathing Caliber Calibration Cancer Patient Cellular biology Chronic Obstructive Airway Disease Clinical Collaborations Communities Computer Simulation Computer software Data Deposition Development Devices Diagnostic Disease Disease Progression Disease model Dose Drug Carriers Drug Delivery Systems Drug Industry Drug Interactions Drug Transport Drug usage Education Effectiveness Electrolytes Ensure Epithelial Escalator Excipients Feedback Formulation Generic Drugs Genetic Geometry Goals Health Healthcare Homeostasis Human In Vitro Life Link Liquid substance Lung Lung diseases Lymph Malignant neoplasm of lung Mechanics Methods Modeling Monitor Morphology Mucociliary Clearance Mucous body substance Patient Education Patients Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Phase Physiological Physiology Population Powder dose form Procedures Process Property Protocols documentation Publishing Pulmonary Function Test/Forced Expiratory Volume 1 Rattus Reporting Research Resolution Respiration Respiratory System Respiratory tract structure Route Running Safety Smooth Muscle Smooth Muscle Myocytes Societies Software Framework Software Tools Structure of parenchyma of lung System Testing Validation Work absorption animal data base bench to bedside biomechanical model care burden computerized tools design drug clearance drug discovery drug inhalation human data improved in vivo insight mobile computing multi-scale modeling multidisciplinary nano nanocarrier nanoparticle novel novel therapeutics particle prototype research study respiratory smooth muscle simulation success tool virtual

项目摘要

DESCRIPTION (provided by applicant): Pulmonary drug delivery has emerged as a noninvasive alternative route for the treatment of lung diseases (asthma, COPD, CF and lung cancer). In order to obtain the desired level of effectiveness and safety of the inhaled drugs, an appropriate deposition on the targeted region and subsequent absorption in the targeted region is vital. Multiscale multidisciplinary computational tools, linking Computational Fluid Dynamics (CFD), particle/species transport and PBPK-PD models, were developed during the Phase I effort for obtaining mechano-biological insights and quantifying the efficacy of the delivery processes. Preliminary results demonstrated the validity and capabilities of this multiscale multidisciplinary computational concept. In Phase II, we will (i) extend the existing particle transport models for handling varied drug sizes, (ii) further develop the deposition formulations for the Reduced Order Models (ROM) for faster than life simulations, (iii) incorporate the airway wall biomechanics model for accurately capturing the dynamics of lumen diameter change, smooth muscle force, particle transport/deposition in healthy and diseased lung states (global or local, levels of progression), (iv) extend and validate the mucosal transport/clearance models on ROM wire meshes to characterize the effects of healthy and diseased states on drug clearance and absorption in the lung tissue, (v) calibrate the models for matching clinical PBPK data for various drugs and administration protocols and (vi) significantly improve the existing GUI for lung geometry alteration (support diseased states) and for the whole-body PBPK. The above aims will hasten the development of pulmonary drugs by carefully identifying key mechanical and biopharmaceutical factors affecting efficacy and safety of inhaled drugs using fast and robust computational simulations. A multistep simulation protocol for modeling drug inhalation delivery, deposition, absorption and PBPK/PD will be established. High fidelity tools will be targeted for pharma expert users and automated fast running reduced order models for pharma end users. The proposed computational toolkit will thus provide a virtual platform to investigate interactions between drug delivery methods, drug/carrier types and the human physiological systems at multiple scales and ultimately optimize the efficacy of pulmonary drug delivery process

描述（由适用提供）：肺部药物输送已成为治疗肺部疾病（哮喘，COPD，CF和肺癌）的无创替代途径。为了获得遗传药物的所需有效性和安全水平，对靶向区域的适当沉积和随后在目标区域的受苦至关重要。多尺度的多学科计算工具，连接计算流体动力学（CFD），粒子/物种传输和PBPK-PD模型，在I阶段的工作期间开发了用于获得机械见解并量化交付过程效率的。初步结果证明了这种多学科计算概念的有效性和能力。在第二阶段，我们将（i）扩展现有的粒子传输模型以处理不同的药物尺寸，（ii）进一步开发了比生命模拟更快的减少订单模型（ROM）的沉积公式，（iii）将气道壁生物力学模型合并，以准确地捕获流明直径的动态和粒子范围，粒子的固定量和静态效力（全球降低）（全球范围）（全球范围）（全球范围）（全球范围） validate the mucosal transport/clearance models on ROM wire meshes to characterize the effects of healthy and disseased states on drug clearance and sufferption in the lung tissue, (v) calibrate the models for matching clinical PBPK data for various drugs and administration protocols and (vi) significantly improve the existing GUI for lung geometry alteration (support disseased states) and for the whole-body PBPK.以上目的将通过仔细识别使用快速和稳健的计算模拟来影响遗传药物的有效性和安全性的关键机械和生物药物因素来开发肺部药物的发展。多步仿真协议高保真工具将针对药物专家用户，并为Pharma最终用户自动运行降低订单模型。因此，拟议的计算工具包将提供一个虚拟平台，以调查药物输送方法，药物/载体类型和人类生理系统之间的相互作用，并最终优化了肺部药物输送过程的效率