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经细胞间途径和汗腺导管途径被动透皮药物扩散的对比研究:衰老的影响。

A comparative study of passive drug diffusion through human skin via intercellular and sweat duct route: effect of aging.

机构信息

Department of Mechanical Engineering, Indian Institute of Technology Bhilai, Bhilai, 491001, India.

Department of Mechanical Engineering and Department of Bioscience & Biomedical Engineering, Indian Institute of Technology Bhilai, Bhilai, 491001, India.

出版信息

Drug Deliv Transl Res. 2024 Sep;14(9):2558-2577. doi: 10.1007/s13346-024-01529-6. Epub 2024 Feb 16.


DOI:10.1007/s13346-024-01529-6
PMID:38363485
Abstract

A method of drug delivery that could provide control over medicine reaching the bloodstream for systemic circulation would be of immense importance. This work presents a comparative study of the temporal and spatial variation of drugs diffusing passively through two separate routes of human skin, namely intercellular (ICR) and sweat duct route (SDR). An analysis is carried out for two age groups (young < 40 years and old > 60 years of age). Governing equations based on Fick's law for mass transfer have been solved numerically using an in-house developed code. The code has been validated thoroughly with numerical and experimental work from the literature. Each skin route is modeled into three compartments sandwiched between the donor and receiver compartments. To understand the role of diffusion and partition coefficient on drug permeation, four drugs, namely hydrocortisone, trans-cinnamic acid, caffeine, and benzoic acid, are considered. The drug diffusion rate is found greater through ICR as compared to SDR. Further, the amount of drugs diffusing through both routes increases with age. Desirable drug characteristic is inferred to be a lower value of partition coefficient and a higher value of diffusion coefficient. This study could lead to real-time assessment of drugs reaching the bloodstream and beyond.

摘要

一种能够控制药物进入体循环的血流的给药方法将具有重要意义。本工作比较研究了药物通过人体皮肤的两种不同途径(细胞间途径(ICR)和汗腺途径(SDR))被动扩散的时空变化。分析了两个年龄组(<40 岁的年轻组和>60 岁的老年组)。基于质量传递的菲克定律的控制方程已使用内部开发的代码进行数值求解。该代码已通过文献中的数值和实验工作进行了彻底验证。每个皮肤途径被建模为三个隔室,夹在供体和受体隔室之间。为了了解扩散和分配系数对药物渗透的作用,考虑了四种药物,即氢化可的松、反式肉桂酸、咖啡因和苯甲酸。与 SDR 相比,ICR 中的药物扩散速度更快。此外,通过两种途径扩散的药物量随年龄增长而增加。推断出理想的药物特性是较低的分配系数和较高的扩散系数。这项研究可以实时评估药物进入血流及其它途径的情况。

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本文引用的文献

[1]
Recent Impact of Microfluidics on Skin Models for Perspiration Simulation.

Membranes (Basel). 2021-2-21

[2]
Aging-related shift of eccrine sweat glands toward the skin surface due to tangling and rotation of the secretory ducts revealed by digital 3D skin reconstruction.

Skin Res Technol. 2021-7

[3]
Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids.

Toxicol In Vitro. 2020-12

[4]
Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities.

Pharmaceutics. 2020-2-13

[5]
Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements.

Mol Pharm. 2018-3-2

[6]
Passive delivery of protein drugs through transdermal route.

Artif Cells Nanomed Biotechnol. 2018-1-29

[7]
Working Up a Good Sweat - The Challenges of Standardising Sweat Collection for Metabolomics Analysis.

Clin Biochem Rev. 2017-2

[8]
Drug delivery to the lungs: challenges and opportunities.

Ther Deliv. 2017-7

[9]
Topical and transdermal delivery of caffeine.

Int J Pharm. 2015-5-21

[10]
Morphology of human sweat ducts observed by optical coherence tomography and their frequency of resonance in the terahertz frequency region.

Sci Rep. 2015-3-13

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