Cited by 22Advancements in Transdermal Drug DeliveryAnimal testing and alternativesDermatology and Skin Diseases

In Vitro and Ex Vivo Models for Screening Topical Anti-Inflammatory Drugs

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Pérez-Salas, Juan Luis, Moreno-Jiménez, Martha Rocío, Rocha-Guzmán, Nuria Elizabeth, González-Laredo, Rubén Francisco, Medina-Torres, Luis, Gallegos-Infante, José Alberto·2023·Scientia Pharmaceutica

Abstract

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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Research works printed but not linked: 3

  1. García Barreno, P. Inflamación. Cienc. Exact. Fís. Nat. 2008, 102, 91-159. Available online: http://www.rac.es/ficheros/doc/0068 1.pdf (accessed on 21 January 2023).
  2. Kindt, T.J.; Goldsby, R.A.; Osborne, B.A.; Kuby, J. Kuby Immunology, 6th ed.; W.H. Freeman: New York, NY, USA, 2007; pp. 350-356.
  3. Sarkar, B.K.; Arya, J.C.; Pal, S.; Dogra, P.; Atteri, S.; Patial, B.; Babu, G.; Meena, A.K. Preparation, standardization and evaluation of preliminary anti-inflammatory activity of herbal formulation of Citrullus colocynthis. J. Adv. Sci. Res. 2021, 12, 127-131.

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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
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

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