The Effects of Nanoparticle Drug Delivery Formulations on the Rheological Properties of Mucus

The aerosol technology used in lungs drug delivery is not precise enough to target all the drugs to alveoli. Some off target deposition of nanoparticles occurs in airway mucus. In general, mucociliary clearance is capable of removing those off target deposition. However, the deposition of nanoparticles on the airway mucus layer could change mucus viscoelastic properties and may alter the dissipation of force through cilia. Thus, it is desirable to understand if the trapped nanoparticles (in off targets) change the normal mucus viscoelastic properties and rheology. Therefore, in this thesis, the viscoelastic properties of mucus are evaluated through oscillatory experiments on the basis of elastic modulus (G ), viscous modulus (G ), phase angle and shear stress developed in the mucus in presence of nanoparticle formulations. It was found that after addition of nanoparticles, G and G of the pig gastric mucus (PGM) increased. However, phase angle of PGM with nanoparticles and PGM control were comparable. The change in moduli of the nanoparticles could be due to interactions between the nanoparticle and mucin. Interestingly, even the addition of just 200µl saline to a mucus, which was previously washed extensively in saline, did change the moduli of mucus. This supported the argument that mucus itself is variable material with aggregates. Nevertheless, it was postulated that the overall changes in moduli and phase angle were not substantial enough to change the rheology of the material. This observation was based on the comparison of phase angles (at different steps of oscillatory experiments), stress developed in the material which remained substantially unchanged and the observation that even addition of 200µl 0.9% saline could slightly change the viscoelasticity. From the observations, it was argued that the off target depositions of nanoparticle do not create substantial changes to viscoelasticity and rheology of the mucus. And, inside the body, even those small observed changes could be handled by homeostasis of the mucociliary clearance. However, these arguments are based on the deposition of single dose of nanoparticles, which may change considerably when multiple doses are administered to the lungs. Moreover, for more conclusive effects on the mucociliary clearance position of the nanoparticles in mucus layer and measurement of dissipation force is required