Optimized Artificial Colonic Mucus Enabling Physiologically Relevant Diffusion Studies of Drugs, Particles, and Delivery Systems.

Development of oral drug delivery systems that penetrate the colonic mucus remains challenging. Artificial models of porcine colonic mucus have been developed that mimic the rheology and viscosity of the native mucus and its contents of mucins, protein, and lipids. However, they are less representative with regard to the zeta potential, a factor of importance for charged molecules and particles. This study therefore aimed to improve the existing porcine artificial colonic mucus model by exchanging the polymer backbone (used for viscosity) to more closely mimic the charge of porcine native colonic mucus. Polymers studied were poly(acrylic acid), hydroxyethylcellulose, sodium hyaluronate, sodium alginate, and pectin. The resulting porcine artificial colonic mucus was assayed for apparent viscosity, storage modulus, pH, water content, zeta potential, and pore size. The two best-performing polymers (poly(acrylic acid) and hydroxyethylcellulose) were then assayed with diffusion of FITC-dextran, particle tracking of nanoparticles, and binding of FITC-dextran and contrasted to data generated in porcine native colonic mucus (PNCM). Of the two polymers, PACM based on HEC generated zeta potential and binding kinetics similar to those of PNCM. We conclude that the choice of polymer in PACMs is critical for improving their use in drug development. The extensive characterization of the PACMs further points toward the importance of complementary techniques to determine rheological characteristics, mesh, and pore size.