Permeability Assessment of a High-Throughput Mucosal Platform

Area of Science:

• Biomedical Engineering
• Pharmacology
• Drug Delivery Systems

Background:

• Drug absorption and distribution are critically dependent on permeability across cellular membranes.
• Existing cell-free in vitro tools inadequately replicate the complex nature of mucosal barriers.
• Drugs must traverse mucus barriers before systemic absorption, posing a significant challenge in drug development.

Purpose of the Study:

• To develop and validate a novel in vitro mucosal platform for high-throughput drug permeability assessment.
• To identify key physicochemical determinants governing drug passive diffusion across mucosal barriers.
• To provide a more predictive model for drug-permeability profiling in early drug development.

Main Methods:

• Utilized a PermeaPad 96-well plate system integrated with a pathological, three-dimensional (3D) mucus model.
• Combined experimental data with computational approaches to analyze drug permeability.
• Investigated the influence of drug physicochemical properties (solubility, size, shape, charge) on permeability.

Main Results:

• Drug solubility, size, and shape were identified as critical factors influencing passive diffusion across the mucosal barrier.
• Drug charge was found to significantly impact interactions with the mucus layer.
• The developed in vitro platform demonstrated potential for high-throughput drug-permeability profiling.

Conclusions:

• The proposed in vitro mucosal platform offers a promising strategy for modeling complex mucosal tissues.
• This platform can enhance the accuracy of drug-permeability profiling, aiding in the selection of viable drug candidates.
• The findings provide valuable insights into the physicochemical properties that govern drug transport across mucosal barriers.