Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Abstract

Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

Effect of viscosity on motion characteristics of bovine sperm

“…The viscosities of the PVP-K90 concentrations are given in Table 1. The viscosity in the actual mucus is in the range of 0.1-1.0 Pa·s, according to the measurements of Lai et al [21]. Therefore, the viscosity used in the present experiment was lower than that in an actual environment by one order of magnitude.…”

“…2). However, the viscosity in mucus is in the range of 0.1-1.0 Pa·s, according to the measurements of Lai et al [21]. Therefore, it is necessary to investigate sperm motility in an environment with a greater viscosity.…”

“…Wolf et al [20] found that the mucus in the uterine tube is a viscoelastic fluid that includes gelatinous materials and macromolecules. Lai et al [21] measured the viscosity of fresh human cervical mucus samples as a function of the shear rate and showed that the viscosity of the mucus was greater than that of water by two or three orders of magnitude, i.e., 0.1-1.0 Pa·s. Furthermore, they indicated that the mucus is a non-Newtonian fluid.…”

Methods to determine the interactions of micro- and nanoparticles with mucus

“…Similarly the concentration of the particle inoculum itself can cause particle aggregation within the matrix [47]. In mucus samples (0.5 g) we have found an inoculum of a 25 µl 0.002% NP suspension to consistently lack aggregation problems.…”

821 Altered Goblet Cell Differentiation and Surface Mucus Properties in Hirschsprung Disease

“…Particle trajectories were generated using tracking algorithm of the ParticleTracker ImageJ plugin [42]. Mean-squared displacements (MSD) and effective diffusivities (D eff ) were determined as previously described [43], [44].…”