In Vitro and Ex Vivo Models for Screening Topical Anti-Inflammatory Drugs
Open accessAbstract
Skin inflammation occurs as an immune response to various stimuli such as ultraviolet light, irritants, or any type of skin barrier injury. Finding safe and effective drugs to combat skin inflammation remains a research challenge. Ethical and legal considerations in animal testing encourage the development of in vitro and ex vivo models for the detection of skin inflammation. This report presents an updated review of non-animal study models available for screening drugs with anti-inflammatory potential. It includes a description of the basic methods used to inhibit protein denaturation and red blood cell membrane stability. Three in vitro inhibition assay methods for enzymes relevant to the skin inflammatory process are then described. The development of cell culture models is described: relatively simple and easy-to-produce two-dimensional (2D) skin cell cultures that allow assessment of response to a given stimulus, three-dimensional (3D) cell cultures that better mimic human skin physiology by more accurately replicating mechanical and chemical signals, and vascularized 3D skin models with dynamic perfusion and microfluidic devices known as skin on a chip. Finally, ex vivo skin models are presented that could more accurately represent human skin in terms of structure, cell signaling mechanisms, and absorption effects. Although the current development of models without the use of animals is promising, improvements and refinements are needed to make the models more suitable as screening platforms for topical anti-inflammatory drugs.
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2D models are not suitable for emulating the relationship between skin and microbiota because they lack the stratum corneum, causing microorganisms to contact proliferating keratinocytes and fibroblasts (which does not happen in vivo), and because bacteria grow faster than human cells, preventing maintenance for more than 24 h.
“Even the 2D models are not suitable for the development of systems capable of emulating the relationship between skin and microbiota. In fact, they lack the stratum corneum, and so the microorganisms would come in direct contact with proliferating keratinocytes and fibroblasts, which does not happen in vivo; moreover, these systems are disadvantaged by the faster growth rate of bacteria compared”
From Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account? (2024) · cites this paper as [28]
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¿Qué son los inflamosomas? El NLRP3 como ejemplo
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Flagged first, then by citations
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A human ex vivo skin model breaking boundaries
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Chitosan non-particulate vaccine delivery systems
Masimov, R., & Wasan, E. K. (2024) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2024.12921 · Cited by 24 · see citing works
Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models
Ribeiro, A. R., Pereira‐Leite, C., Rosado, C., Aruci, E., Colley, H. E., Krohn, I. K., Baldea, I., Pantelić, I., Fluhr, J. W., Simões, S., et al. (2024) · JID Innovations · doi:10.1016/j.xjidi.2024.100340 · Cited by 12 · see citing works
Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account?
Galvan, A., Pellicciari, C., & Calderan, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021165 · Cited by 11 · see citing works
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- Authors
- Pérez-Salas, J. L., Moreno-Jiménez, M. R., Rocha-Guzmán, N. E., González-Laredo, R. F., Medina-Torres, L., & Gallegos-Infante, J. A.
- Affiliations
- TecNM/Instituto Tecnológico de Durango, UPIDET, Blvd Felipe Pescador 1830 Ote, Col Nueva Vizcaya, Durango 34080, Mexico
- Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
- Venue
- Scientia Pharmaceutica
- Publisher
- MDPI AG
- Published
- 2023-04-17
- Volume
- 91
- Issue
- 2
- Pages
- 20
- ISSN
- 0036-8709 (ISSN-L)
- 2218-0532
- OpenAlex
- W4366282684
- Cited by
- 22
- References
- 98
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 1
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientia Pharmaceutica (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- TecNM (13987.22-P)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- topical anti-inflammatory drugs, skin inflammation, in vitro skin model, ex vivo skin model, alternatives to animal testing, skin-on-a-chip, microfluidics, enzyme inhibition assay, protein denaturation, red blood cell membrane stability, drug screening
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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