In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.
In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.
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DOI：
10.1007/s11095-022-03423-7
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发表时间：
2023-01
影响因子：
3.7
通讯作者：
Chen, Tao
中科院分区：
文献类型：
--
作者：
Sebastia-Saez, Daniel;Benaouda, Faiza;Lim, Chui Hua;Lian, Guoping;Jones, Stuart A.;Cui, Liang;Chen, Tao
开发一个模拟模型，以探索局部施加低压下机械拉伸和大分子扩散到皮肤中之间的相互作用，这是一种新的渗透增强方法。采用有限元法模拟皮肤的机械变形和分子扩散过程，并通过体外透皮实验进行验证。采用数值模拟和实验数据相结合的方法研究了局部低压下大分子物质的经皮渗透。机械模拟导致皮肤拉伸和变薄（毛囊直径增加20%-26%，皮肤厚度减少21%-27%）。在有和没有低压的情况下，角质层中葡聚糖的浓度低于检测限。活表皮和真皮中的浓度不受低压影响（约2 μg cm-2）。渗透到受体流体中的能力从大气压下的检测限以下大幅增强到低压下的6 μg cm-2。模拟结果与大气条件下的实验结果相比令人满意。在低压下，当皮肤层中右旋糖酐的扩散系数从10 μm2 s-1增加到200-500 μm2 s-1之间时，可以获得令人满意的比较。应用低压引起皮肤机械拉伸和扩大毛囊。仅这种增大不能令人满意地解释低压下经皮渗透进入受体液体的增加。来自计算机模拟的结果表明，施加低压增加了皮肤中的扩散，这导致改善的整体透皮渗透。
To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method. Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure. Mechanical simulations resulted in skin stretching and thinning (20%–26% hair follicle diameter increase, and 21%–27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 μg cm−2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 μg cm−2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from 10 μm2 s−1 to between 200–500 μm2 s−1. Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation.
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应用共聚焦拉曼显微镜表征局部半固体制剂及其对人体皮肤的体外渗透。
影响因子：
3.7
作者：
Jung, Nathalie;Namjoshi, Sarika;Mohammed, Yousuf;Grice, Jeffrey E.;Benson, Heather A. E.;Raney, Sam G.;Roberts, Michael S.;Windbergs, Maike
通讯作者：
Windbergs, Maike
影响因子：
10.4
作者：
Tinkle, SS;Antonini, JM;Adkins, EJ
通讯作者：
Adkins, EJ
影响因子：
5.8
作者：
Wang, Liming;Chen, Longjian;Han, Lujia
通讯作者：
Han, Lujia
DOI：
10.1073/pnas.2120340119
发表时间：
2022-05-03
影响因子：
11.1
作者：
Benaouda, Faiza;Inacio, Ricardo;Lim, Chui Hua;Park, Haeeun;Pitcher, Thomas;Alhnan, Mohamed A.;Aly, Mazen M. S.;Al-Jamal, Khuloud;Chan, Ka-lung;Gala, Rikhav P.;Sebastia-Saez, Daniel;Cui, Liang;Chen, Tao;Keeble, Julie;Jones, Stuart A.
通讯作者：
Jones, Stuart A.
DOI：
10.1016/j.jconrel.2016.01.052
发表时间：
2016-03-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Inacio R;Poland S;Cai XJ;Cleary SJ;Ameer-Beg S;Keeble J;Jones SA
通讯作者：
Jones SA