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针对具有半球形肿瘤的四代肺气道模型的靶向药物气溶胶沉积分析。

Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors.

作者信息

Kleinstreuer C, Zhang Z

机构信息

Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA.

出版信息

J Biomech Eng. 2003 Apr;125(2):197-206. doi: 10.1115/1.1543548.

Abstract

One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of "controlled particle release and targeting" is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R approximately 1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.

摘要

一个受到广泛关注的重要研究领域是开发高效的药物递送系统,以实现药物在期望部位的沉积和摄取。例如,控制药物气雾剂的释放并使其靶向肺部的特定区域是对抗肺部疾病、糖尿病、病毒感染、癌症等的一种新方法。确定可行的空气颗粒流是开发此类递送装置(如智能吸入器)的先决条件。本文引入了“控制颗粒释放和靶向”的概念,并针对患有不同大小和位置的半球形肿瘤的支气管肺气道代表性模型讨论了结果。结果表明,在正常颗粒入口条件下,对于临界半径r/R约为1.25的特定肿瘤表面,颗粒质量分数最高仅可达11%,而对于入口斯托克斯数和雷诺数的实际组合,控制颗粒释放可实现35%至92%的沉积分数,这主要取决于肿瘤大小。此外,通过控制释放和靶向方法,附近的健康组织几乎不会受到通常具有侵袭性的药物气雾剂的影响。假设在依次分叉的刚性气道中存在层流、准稳态、三维气流和球形非相互作用的微米级颗粒,使用经过验证的商业有限体积代码以及在高端工程工作站上的用户增强程序获得了结果。这个新概念具有通用性,因此也应该适用于呼吸系统的其他区域。

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