Transport and distribution of biotherapeutics in different tissue layers after subcutaneous injection

Rahimi, Ehsan; Gómez, Héctor; Ardekani, Arezoo M.

doi:10.1016/j.ijpharm.2022.122125

Cited by 15 publications

(2 citation statements)

References 48 publications

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“…1d,e are already appropriate for the homogenized response given that the macroscale behavior is dictated by the dermis, particularly under larger deformations, as is usually argued in models of the skin as a homogeneous material [29,23,34]. Multi-layer models are necessary for particular applications such as drug delivery or skin tribology [11,39]. Here we show that the addition of the sinusoidal interface leads to specific patterns of stress/strain concentration which, beyond implications for fracture, might play a role in skin mechanobiology.…”

Section: Discussionmentioning

confidence: 99%

The Role of Interface Geometry and Appendages on the Mesoscale Mechanics of the Skin

Moreno-Flores

Rausch

Tepole

2023

Preprint

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The skin is the largest organ in the human body and serves various functions, including mechanical protection and mechanosensation. Yet, even though skin's biomechanics are attributed to two main layers -epidermis and dermis- computational models have often treated this tissue as a thin homogeneous material or, when considering multiple layers, have ignored the most prominent heterogeneities of skin seen at the mesoscale. Here we create finite element models of representative volume elements (RVEs) of skin, including the three-dimensional variation of the interface between the epidermis and dermis as well as considering the presence of hair follicles. The sinusoidal interface, which approximates the anatomical features known as Rete ridges, does not affect the homogenized mechanical response of the RVE but contributes to stress concentration, particularly at the valleys of the Rete ridges. The stress profile is three-dimensional due to the skin’s anisotropy, leading to high-stress bands connecting the valleys of the Rete ridges through one type of saddle point. The peaks of the Rete ridges and the other class of saddle points of the sinusoidal surface form a second set of low-stress bands under equi-biaxial loading. Another prominent feature of the heterogeneous stress pattern is a switch in the stress jump across the interface, which becomes lower with respect to the flat interface at increasing deformations. These features are seen in both tension and shear loading. The RVE with the hair follicle showed strains concentrating at the epidermis adjacent to the hair follicle, the epithelial tissue surrounding the hair right below the epidermis, and the bulb or base region of the hair follicle. The regions of strain concentration near the hair follicle in equi-biaxial and shear loading align with the presence of distinct mechanoreceptors in the skin, except for the bulb or base region. This study highlights the importance of skin heterogeneities, particularly its potential mechanophysiological role in the sense of touch and the prevention of skin delamination.

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Section: Discussionmentioning

confidence: 99%

The Role of Interface Geometry and Appendages on the Mesoscale Mechanics of the Skin

Moreno-Flores

Rausch

Tepole

2023

Preprint

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“…This can affect the ease with which a needle can penetrate the skin and deliver the therapeutic drug after the injection. Hence, a stiffer dermis increases the resistance of the skin to needle penetration, affecting drug transport and distribution and potentially leading to injection errors or discomfort for the patient [5]. The needle length and the hypodermis (SC thickness) impact the drug distribution [1, 6, 7].…”

Section: Introductionmentioning

confidence: 99%

Rheological and Lipid Characterization of Minipig and Human Skin Tissue: A Comparative Study Across Different Locations and Depths

Mitra,

Nonamaker,

Cordera

et al. 2024

Preprint

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Understanding the rheology of minipig and human skin is crucial for enhancing drug delivery methods, particularly for injections. Despite many studies on skin's viscoelasticity, especially the subcutaneous layer, comparative analyses across different clinical sites are scarce, as is data on the impact of hydration or lipid levels. This study employs shear rheology and lipid analysis to evaluate viscoelasticity and lipid content across three anatomical locations-breast, belly, and neck and three different depth layers in Yucatan minipigs. It reports on how viscoelastic properties change with frequency, time, and strain, noting strain-stiffening and shear-thinning at high strain amplitudes. Human male and female abdominal tissues are also compared to minipig tissues, highlighting distinct viscoelastic traits and lipid's role in them. The findings suggest the existence of species, anatomical location, tissue depth, and sex-based rheological differences. We also concluded the minipig male tissue is a more accurate model for human male subcutaneous tissue than for females.

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Computational modeling of the effect of skin pinch and stretch on subcutaneous injection of monoclonal antibodies using autoinjector devices

Lucio

Leng

Wang

et al. 2023

Biomech Model Mechanobiol

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Transport and distribution of biotherapeutics in different tissue layers after subcutaneous injection

Cited by 15 publications

References 48 publications

The Role of Interface Geometry and Appendages on the Mesoscale Mechanics of the Skin

The Role of Interface Geometry and Appendages on the Mesoscale Mechanics of the Skin

Rheological and Lipid Characterization of Minipig and Human Skin Tissue: A Comparative Study Across Different Locations and Depths

Computational modeling of the effect of skin pinch and stretch on subcutaneous injection of monoclonal antibodies using autoinjector devices

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