Hyaluronate spreading validates mucin-agarose analogs as test systems to replace porcine nasal mucosa explants: An experimental and theoretical investigation

Abstract

To rationally design intranasal drug delivery systems, i.e., for the assessment of the administered formulation properties, ex vivo porcine nasal mucosa (PNM) explants are one modern but complex standard. Therefore, the development of artificial mucosa substrates as straight-forward PNM analogs is important. The mucosa analog (MA; 5 wt% mucin and 1 wt% agarose coating on glass) was found to be a sufficient substitute of PNM. It exhibited similar mucoadhesive properties as determined by detachment force measurements (MA: 0.04 ± 0.01 N mm; PNM: 0.03 ± 0.01 N mm) and its’ topological surface properties (i.e., roughness ratio r, and mean arithmetic surface height Sa) were in good agreement with the natural tissue (rMA: 1.12, rPNM: 1.17; Sa,MA: 7.80 ± 1.95 µm, Sa,PNM: 7.61 ± 0.72 µm). Using this MA, the present study describes an experimental and theoretical spreading approach using hyaluronic acid (HA) in various concentrations (10–30 mg mL−1), molecular weights (280–1260 kDa), and tyramine modifications (HA-Tyr). The spreading behavior of HA and HA-Tyr was determined in different environments (laboratory conditions, climatic chamber) on specific substrates (PNM, artificial mucosa, and glass). An exponential relationship between HA concentration and viscosity was determined. Higher humidity, use of HA-Tyr, and sessile droplet orientation improved spreading. The dynamic spreading model was then developed mathematically and validated experimentally. Parameters such as molecular weight, droplet volume, and surface tension are also covered by this mathematical model. The present study demonstrates that this MA combines attractive features such as broad availability, good reproducibility, high stability under physiological conditions, ease of fabrication and low production cost.