Mucus models to evaluate the diffusion of drugs and particles

Abstract

Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.

Commercial Porcine Gastric Mucin Preparations, also Used as Artificial Saliva, are a Rich Source for the Lectin TFF2: In Vitro Binding Studies

“…The topological organization of MUC6 oligomers is probably of importance for the permeability of gastric mucus. This might also influence the absorption of nutrients and drug delivery . Furthermore, TFF2 together with MUC6 might also be involved in the phenomenon of “viscous fingering”, which is observed if hydrochloric acid penetrates gastric mucus .…”

“…We have investigated for the first time two different commercial porcine gastric mucin preparations for their TFF2 contents. In the past, they were extensively studied as model systems to understand the microstructure and complex rheology of gastric mucus . Furthermore, one preparation is also sold as a saliva substitute .…”

Measuring the administered dose of particles on the facial mucosa of a realistic human model

“…Veres concluded that inhaled environmental allergens may induce aberrant activation of immune cells in the airway mucosa, resulting in allergic airway disease. Studies of the side effects of drug delivery have also shown that penetration of particulates through mucus poses a potential risk to human health . Nanocarriers are normally used in drug delivery because they can penetrate quickly through mucus to reach the underlying cells.…”

“…Our model did not include goblet cells, mucus secretory cells, or submucosal glands to produce mucosal lining fluid (ie, mucus) . Mucin is the main structural component of mucus; these components interact with each other and with other components of mucus to form a meshlike structure . In addition to this meshlike structure, mucus captures foreign particles via an adhesion effect.…”

“…An accurate and quantitative measure of the causal relationship between exposure and health outcomes would certainly benefit the development of effective control strategies, but such a measure is beyond the resolution of common epidemiologic studies. In vitro methods such as cell or animal models can implement partial pathological evidence of damage to genes, tissues, and organs, but their lack of individual susceptibility limits definitive conclusions for population subgroups. In contrast, biomarkers that indicate oxidative stress, inflammation, thrombosis, and many other health outcomes reflect individual susceptibility, but uncertainty remains due to disturbances from uncontrolled confounders.…”