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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Optimized Artificial Colonic Mucus Enabling Physiologically Relevant Diffusion Studies of Drugs, Particles, and
Marco Tjakra1,2, Nopdanai Chakrapeesirisuk1, Magdalena Jacobson3
1Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.
Molecular Pharmaceutics
|June 10, 2025
Summary
Developing artificial mucus models for drug delivery is crucial. This study improved a porcine mucus model by optimizing polymer choice, enhancing its charge properties for better drug development applications.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Mucosal Research
Background:
- Developing oral drug delivery systems that effectively penetrate colonic mucus is a significant challenge.
- Existing artificial models of porcine colonic mucus mimic rheology and viscosity but lack accurate zeta potential representation.
- Zeta potential is critical for the behavior of charged molecules and particles within mucus.
Purpose of the Study:
- To enhance the existing artificial porcine colonic mucus model by modifying its polymer backbone.
- To improve the model's charge characteristics to better mimic native porcine colonic mucus (PNCM).
- To evaluate the suitability of the improved model for drug development applications.
Main Methods:
- Synthesized artificial porcine colonic mucus (PACM) models using various polymers: poly(acrylic acid), hydroxyethylcellulose, sodium hyaluronate, sodium alginate, and pectin.
- Characterized PACMs for rheological properties (viscosity, storage modulus), pH, water content, zeta potential, and pore size.
- Assessed the performance of the two best-performing PACMs (poly(acrylic acid)-based and hydroxyethylcellulose-based) using FITC-dextran diffusion, nanoparticle tracking, and binding kinetics, comparing results to PNCM.
Main Results:
- Poly(acrylic acid) and hydroxyethylcellulose were identified as the most promising polymers for improving the artificial mucus model.
- The PACM model utilizing hydroxyethylcellulose (HEC) demonstrated zeta potential and binding kinetics closely resembling those of PNCM.
- Extensive characterization highlighted the importance of complementary techniques for evaluating rheological properties, mesh, and pore size.
Conclusions:
- The selection of the polymer backbone is critical for developing accurate and effective artificial colonic mucus models.
- The improved PACM, particularly the HEC-based version, offers a more representative model for studying drug transport and binding in the colon.
- This advancement is vital for enhancing the development of oral drug delivery systems targeting the colonic mucus layer.
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