Human skin models: From healthy to disease‐mimetic systems; characteristics and applications

Abstract

Skin drug delivery is an emerging route in drug development, leading to an urgent need to understand the behaviour of active pharmaceutical ingredients within the skin. Given, As one of the body's first natural defences, the barrier properties of skin provide an obstacle to the successful outcome of any skin drug therapy. To elucidate the mechanisms underlying this barrier, reductionist strategies have designed several models with different levels of complexity, using non‐biological and biological components. Besides the detail of information and resemblance to human skin in vivo, offered by each in vitro model, the technical and economic efforts involved must also be considered when selecting the most suitable model. This review provides an outline of the commonly used skin models, including healthy and diseased conditions, in‐house developed and commercialized models, their advantages and limitations, and an overview of the new trends in skin‐engineered models.

Protocol for the Isolation of Stratum Corneum from Pig Ear Skin: Evaluation of the Trypsin Digestion Conditions

“…Different approaches have been considered, from the most simplistic non-lipid models to more complex in vitro lipid-based systems, as well as cell-based approaches, or even ex vivo human or animals skin mimetics. Some models mimic just epidermis or both dermis and epidermis, while more complex approaches include the hypodermis components and also comprise the incorporation of various skin components in the models [ 1 ].…”

“…Even though the skin is a complex organ composed by several layers [ 2 ], many stratum corneum ( SC )-based models have been proposed (reviewed in [ 1 ]). These approaches are simpler than full-thickness skin mimetic models, however they represent a valuable approximation for the prediction of drugs´ permeation across the skin.…”

“…Due to the lipid nature of the SC , some in vitro models [ 1 ] considered the use of lipids or liposomes as main constituents of the mimetic membranes, respectively, known as PAMPA [ 8 , 9 ] (Parallel Artificial Membrane Permeability Assay) or PVPA (Phospholipid Vesicle-based Permeation Assay) [ 10 ] systems. Alternatively, another approach has been introduced, the Permeapad ® model [ 11 ].…”

“…Amongst the several reported ex vivo skin mimetic models, pig skin models are probably the most utilized due to their biological similarities with the human skin, as extensively discussed in [ 1 ]. Pig ear models have great similarities with the human skin particularly regarding the anatomical, physiological, and histological characteristics, mainly the layers’ thickness, similarity in hair follicle, blood vessel density and lipid, collagen, and elastin content of SC .…”

“…Particularly due to the analogy with human skin layers, the central outside part of the ear is the most suitable for mimetic purposes from different parts of the pig body. Moreover, the permeability of both human and pig skin is quite similar, mainly for hydrophobic drugs (reviewed in [ 1 ]). Ex vivo SC mimetic models usually comprise the isolation of this layer from human or animal (pig) skin samples, however the isolation protocols are very distinct thus might hamper data correlation between publications.…”