Taking Particle Tracking into Practice by Novel Software and Screening Approach: Case-Study of Oral Lipid Nanocarriers.

The success on the design of new oral nanocarriers greatly depends on the identification of the best physicochemical properties that would allow their diffusion across the mucus layer that protects the intestinal epithelium. In this context, particle tracking (PT) has arisen in the pharmaceutical field as an excellent tool to evaluate the diffusion of individual particles across the intestinal mucus. In PT, the trajectories of individual particles are characterized by the mean square displacement ( MSD ), which is used to calculate the coefficient of diffusion ( D ) and the anomalous diffusion parameter ( α ) as MSD=4Dτα. Unfortunately, there is no stablished criteria to evaluate the goodness-of-fit of the experimental data to the mathematical model. This work shows that the commonly used R ² parameter may lead to an overestimation of the diffusion capacity of oral nanocarriers. We propose a screening approach based on a combination of R ² with further statistical parameters. We have analyzed the effect of this approach to study the intestinal mucodiffusion of lipid oral nanocarriers, compared to the conventional screening approach. Last, we have developed software able to perform the whole PT analysis in a time-saving, user-friendly, and rational fashion.