Multimaging™ Applied to Skin Distribution Study: Applications in Dermatology for Pharmaceuticals and Cosmetics from Discovery to Clinical

Introduction:

In pharmacology, drugs can be applied to skin for two purposes: 1) to directly treat disorders of the skin 2) to deliver drugs to other tissues (i.e transdermal application). Cosmetics (care substances) can also be applied to skin; however, they are typically used to enhance the appearance of the human skin. Care substances are generally mixtures of chemical compounds; with some being derived from natural sources and many being synthetics. Knowledge of different forms and physicochemical properties of compounds, as well as understanding the nature of the skin, are important as all these parameters can affect percutaneous compound absorption (shunt diffusion, permeation or penetration). Understanding the biological principles and metabolism is essential for their effective and safe use. In addition, understanding the proper molecular formulation will not only improve the efficacy of these compounds, but it will also save money.

Effective and safe use of topical agents requires appreciation of the physiological variables that influence the interactions of drugs and the skin, impacting absorption and transport. The skin is a multi-compartment tissue affected in numerous ways by both diseases and their treatments. The bulk of percutaneous absorption for most agents is through the stratum corneum. Epidermal structure and the role of hair follicles and sweat glands, as pathways for absorption, are also crucial for the absorption of drugs and care substances.
In order to study the diffusion of compounds in the skin, an in vitro diffusion system called the Franz diffusion cell (FD-C) is the primary reference of today.

Nevertheless, this approach gives only some information about the compound quantity which has passed through the tissue. In addition, the impact of the absorbed compounds on histological regions is not clearly correlated and determined. Quantitative predictions of molecular transport rates through the skin are key to the development of topically applied and transdermally delivered drugs, as well as risk assessment associated with dermal exposure. That is why liquid chromatography coupled to mass spectrometry (LC-MS) approaches are also performed on skin tissues: compound concentrations are calculated for the whole homogenized tissue or on isolated tissue slices from the epidermis to the hypodermis (which is time consuming). Once again, it is difficult to correlate the compound accumulation within a specific histological structure; as well as, to generate an understanding of the molecular distribution.

For this reason, the combination of images from standard histology, immunohistochemistry (IHC), microscopy, and quantitative mass spectrometry imaging (QMSI) allows for an individual to correlate the compound distribution and concentration within histological structures. We apply Multimaging™, a multi-imaging approach, to several dermatological applications such as penetration pathway studies, target engagement validations, screening of compounds and/or formulations, and pharmacodynamics studies which monitors the effects of the compound…

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