Understanding Drug Delivery Outcomes: Progress in Microscopic Modeling of Skin Barrier Property, Permeation Pathway, Dermatopharmacokinetics, and Bioavailability

Lian, Guoping; Chen, Tao; Kattou, Panayiotis; Yang, Sen; Li, Lingyi; Han, Lujia

doi:10.1002/9781119769644.ch7

Cited by 3 publications

(4 citation statements)

References 70 publications

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“…Bioavailability corresponds to the speed and extent of the passage of the active principle (drug or metabolite) into the general circulation, thus reaching the site of action (46). The bioavailability of active ingredients in dermal preparations is a key factor (47). In our work, it was revealed that phenolic compounds with high skin permeability were not associated with high bioavailability scores.…”

Section: Discussionmentioning

confidence: 64%

Phenolic Compounds and Skin Permeability: An In Silico Investigation

Hammami

Chaabani

Yeddess

et al. 2023

Avicenna J Med Biochem

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Background: The skin is the largest organ of the body and provides the main barrier between the internal and external environment. Assessment of skin permeability is of critical importance for understanding and predicting in vivo efficacy and bioavailability of bioactive phenolic compounds. Objectives: This study investigated the relationship between skin permeability and phenolic compounds using in silico methods. Methods: Screening of skin permeability was performed on 475 randomly selected phenolic compounds. Molecules were expressed in SMILE format downloaded from Phenol-Explorer Database (version 3.6, 2016). Then, their skin permeability was determined by the linear model of the quantitative structure-activity relationship (QSAR). The obtained results were investigated for normal distribution and correlation with pharmacological properties. Results: Our investigation showed that ferulate hydroxycinnamic acid derivatives were the most important phenolic subclass with a permeability of -1.65 cm/s. The relationship between permeability and lipophilicity, water solubility, synthetic accessibility, and bioavailability was evaluated. The statistical analysis revealed that the highest skin permeability was associated with three parameters: the topological polar surface area (TPSA), molecular weight, and lipophilicity (iLog P). Conclusion: The cutaneous permeability depended on several chemical parameters of the molecule used. The classification of phenolic compounds according to their structures proved a wide variability in this permeability.

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Section: Discussionmentioning

confidence: 64%

Phenolic Compounds and Skin Permeability: An In Silico Investigation

Hammami

Chaabani

Yeddess

et al. 2023

Avicenna J Med Biochem

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“…The model for transdermal permeation of large molecules solves the diffusion equation for each layer of the skin [18,19] where c i is the concentration in a specific (the i-th) layer of the skin (e.g., stratum corneum, viable epidermis, et cetera), t denotes time and � ⃗ J corresponds to Fick's diffusive flux:…”

Section: In-silico Modelling Of Transdermal Permeationmentioning

confidence: 99%

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

et al. 2022

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Objectives 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. Methods 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. Results 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 $$\bullet$$ ∙ cm−2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 μg $$\bullet$$ ∙ 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 $$\sim$$ ∼ 10 μm2$$\bullet$$ ∙ s−1 to between 200–500 μm2$$\bullet$$ ∙ s−1. Conclusions 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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“…Thus, the stratum corneum is considered the main barrier to the permeation of drugs through the skin. 22,23 In situations in which this barrier is broken (such as in injuries caused by cuts and/or burns) or when the homeostasis balance is altered, skin diseases or even systemic diseases can occur. 19 In the innermost part of the epidermis, in turn, less differentiated cells are found.…”

Section: Skin Structurementioning

confidence: 99%

“…The stratum corneum is one of the main responsible for the skin's barrier effect, controlling the permeation of substances through the skin. Thus, the stratum corneum is considered the main barrier to the permeation of drugs through the skin 22,23 . In situations in which this barrier is broken (such as in injuries caused by cuts and/or burns) or when the homeostasis balance is altered, skin diseases or even systemic diseases can occur 19 …”

Section: Skinmentioning

confidence: 99%

Dressing systems based on chitosan as active transport platforms in the treatment of burnt skin: Mini‐review

Muniz

Menezes

2022

Polymers for Advanced Techs

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Burns are one of the most common injuries worldwide, affecting thousands of people every year. These wounds, when more severe, can pose a risk to the individual's systemic health and lead to many hospital visits. Among the possible complications arising from cases of deep or generalized burns, sepsis, scar tissue contraction after inadequate healing, and burn shock caused by hypovolemia stand out. Burnt skin is extremely susceptible to bacteria and other pathogens, due to the loss of the protection provided by intact layers of skin, which can severely hinder its proper healing. Several strategies can be used to treat these injuries, among which, the use of hydrogel‐based dressings stands out because of the wet wound healing process. Thus, many studies have focused on the therapeutic effects of chitosan‐based hydrogels for better wound healing due to the good characteristics of this matrix, which include the high biocompatibility, antimicrobial activity, and ability to act as a carrier for the local delivery of actives. In this perspective, studies that explore hydrogel formulations containing chitosan showed the high versatility of these systems that have already been used as transport platforms for natural actives, biomolecules, synthetic antimicrobials, and even antimicrobial nanoparticles. The results of these studies indicate that the use of dressings based on hydrogels containing chitosan can accelerate the healing of wounds caused by burns in the animal model and achieve synergistic antimicrobial effects with some actives, indicating that chitosan hydrogels hold great promise in developing healing systems to regenerate burnt skin

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Understanding Drug Delivery Outcomes: Progress in Microscopic Modeling of Skin Barrier Property, Permeation Pathway, Dermatopharmacokinetics, and Bioavailability

Cited by 3 publications

References 70 publications

Phenolic Compounds and Skin Permeability: An In Silico Investigation

Phenolic Compounds and Skin Permeability: An In Silico Investigation

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

Dressing systems based on chitosan as active transport platforms in the treatment of burnt skin: Mini‐review

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