Chapter 3.1 - Cell-based in vitro models for buccal permeability studies

Abstract

The oral route is the most common route for drug administration due to the high patient compliance and associated low costs. However, drugs administered by the oral route are exposed to the harsh environment of the gastrointestinal tract and the first-pass metabolism in the liver, which can interfere with their bioavailability. When drugs are administered by buccal route, those problems may be overcome, since drugs are directly absorbed via the internal jugular vein, reaching faster the systemic circulation. As result, the doses required to achieve the therapeutic effect are lower, which could reduce the side effects. Considering that, buccal mucosa has been used as a promising site for local and systemic drug delivery. In vivo and ex vivo models are commonly used to evaluate the permeability and toxicity of compounds through buccal mucosa; however, these models have some limitations, namely, high cost, interindividual variability, time consuming, and ethical concerns. In this sense, there is an urgent need to develop in vitro cell-based models that overcome these drawbacks and better resemble human buccal mucosa. Several two-dimensional (2D) and three-dimensional (3D) buccal tissue models were developed over the years to study the buccal permeability and toxicity of drugs and infectious diseases. Nonetheless, the in vitro buccal models developed until the moment do not fully represent the human buccal tissue, due to the absence of a mucus layer, and vascular and immunological components.