Advances in the Evaluation of Gastrointestinal Absorption Considering the Mucus Layer

Abstract

Because of the increasing sophistication of formulation technology and the increasing polymerization of compounds directed toward undruggable drug targets, the influence of the mucus layer on gastrointestinal drug absorption has received renewed attention. Therefore, understanding the complex structure of the mucus layer containing highly glycosylated glycoprotein mucins, lipids bound to the mucins, and water held by glycans interacting with each other is critical. Recent advances in cell culture and engineering techniques have led to the development of evaluation systems that closely mimic the ecological environment and have been applied to the evaluation of gastrointestinal drug absorption while considering the mucus layer. This review provides a better understanding of the mucus layer components and the gastrointestinal tract’s biological defense barrier, selects an assessment system for drug absorption in the mucus layer based on evaluation objectives, and discusses the overview and features of each assessment system.

Assessment of polymeric mucin–drug interactions

“…We have demonstrated potential interactions between human mucins and various drugs by relatively simple and rapid methods. The interaction of mucins with drugs has attracted much interest in the field of drug discovery research [ 6 , 7 , 23 , 25 ]. Going forward, it will be important to evaluate interactions with mucins in more detail for example using microscopy methods (TEM, AFM) and rheological studies, and there is a need to further develop evaluation systems that enable the rapid assessment of interactions.…”

“…Moreover, the complex chemical structure of mucins, such as highly O-glycosylated hydrophilic central mucin domains and non-O-glycosylated cysteine-rich hydrophobic protein regions, can also act as a selective physicochemical barrier and provides binding sites (hydrophobic or electrostatic binding) [ 2 , 5 ]. Recently, there has been considerable interest in the interactions between mucins and drug compounds in terms of whether the mucus barrier plays an important role in efficient mucosal drug absorption [ 6 , 7 ].…”