Modeling Drug Absorption from the Dermis after an Injection

Zhi, Li; Biswas, Abhijit; Finkelstein, Joshua; Grein, Stephan; Kapoor, Yash; Milewski, Mikolaj; Queisser, Gillian

doi:10.1016/j.xphs.2020.10.042

Cited by 4 publications

(5 citation statements)

References 40 publications

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“…The reasons for the different results in the numerical simulation and experimental data comparison in the three drug delivery system may be as follows: in the transdermal delivery model, the drug delivery matrix and skin are assumed to be homogeneous isotropic materials, but in fact, the skin is composed of the cuticle, epidermis, and dermis. It is clear that its diffusion coefficient is not a constant, and the drug concentration measurement by microdialysis is generally located in the dermis [ 21 , 22 , 23 ]. Therefore, the numerical simulation results and experimental results will exhibit certain deviations.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Study of Triptolide Nanocarrier in Transdermal Drug Delivery System—Combination of Experiment and Mathematical Modeling

et al. 2023

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Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the “first pass effect” of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin–blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three−layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Study of Triptolide Nanocarrier in Transdermal Drug Delivery System—Combination of Experiment and Mathematical Modeling

et al. 2023

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“…The thickness of the lymphatic membrane is denoted as d l . We use an exponential function to represent the variation of opening width w with the pressure difference between the interstitial pressure and the lymphatics ∆p = p i − p l [26,44].…”

Section: Transvascular Fluid Flow and Solute Transportmentioning

confidence: 99%

“…The opening width of the primary valves on the lymphatic vessels w is 10∼40 nm at the basal pressure and the width of the opening slit can reach as high as 64 nm at high interstitial pressure due to the injection according to the simulations in [44]. The baseline values for the parameters in the improved Kedem-Katchalsky model are shown in Table 1 [26,27,44,45]. The tissue and solute properties (such as hydraulic permeability and solute size) and injection process parameters (such as injection duration and volume) are inputs needed for the computational model, as shown in Figure 2.…”

Section: Transvascular Fluid Flow and Solute Transportmentioning

confidence: 99%

“…In our previous work [13], three different transport conditions are used to investigate solute transport across the lymphatic vessel membrane, including the Kedem-Katchalsky model. In [26,27], an integral form of the modified Kedem-Katchalsky formulation is used to study dermal clearance through the blood and lymphatic vessels. To further address the special physiological structure of the lymphatic vessel membrane, in this paper, we develop an improved Kedem-Katchalsky model for solute transport across the explicit lymphatic vessel wall.…”

Section: Introductionmentioning

confidence: 99%

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Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue

Han

Huang

Rahimi

et al. 2023

Biology

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Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. An improved Kedem–Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. At last, the effect of different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. In this paper, we provide a novel and time-efficient computational model for solute transport across the lymphatic vasculature connecting the microscopic properties of the lymphatic vessel membrane to the macroscopic drug absorption.

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“…where the effect the capillaries had on partitioning and diffusion was analyzed. The impact of the lymphatic vessels was also considered in these models, and lymphatic absorption after dermal injection has been recently modelled by Li et al [21]. A physiological interpretation of the capillaries was recently investigated in Calcutt and Anissimov [22].…”

Section: Introductionmentioning

confidence: 99%