Combined Experimental Modeling Approach Research Articles

Simulating kinetic parameters in transporter mediated permeability across Caco-2 cells. A case study of estrone-3-sulfate

Substances that compete for the same saturable intestinal transporters may when dosed together lead to altered permeability and hence influence bioavailability. The aim was to simulate kinetic parameters, i.e. K m and J max, for transporter mediated E 1S permeability across Caco-2 cells by a combined experimental modeling approach. 4 classes of transporters were suggested to be involved in the permeability of E 1S, i.e. apical influx (T I) and efflux (T III) as well as basolateral efflux (T II) and influx (T IV). Efflux ratio of E 1S was determined to 6.8. E 1S is suggested to have highest affinity to T III. T IV is however suggested to be rate limiting in exsorptive P APP due to lower J max of T IV, compared to T III. Possible interactions between E 1S and the excipients erythrosine and Brij35 on these 4 classes of transporters were also studied. From these studies it is suggested that erythrosine does interact with E 1S on apical efflux transporter T III by competitive inhibition. Furthermore interaction between erythrosine and E 1S is suggested on apical influx transporter (T I). Brij35 does not seem to interact with E 1S on apical transporters. The present model seem to be a valuable tool to simulate kinetic parameters for compounds being substrates to multiple transporters as well as to estimate kinetic parameters for compounds interacting on the same transporters.

Computational battery dynamics (CBD)—electrochemical/thermal coupled modeling and multi-scale modeling

This paper reviews the development of first-principles based mathematical models for batteries developed on a framework parallel to computation fluid dynamics (CFD), herein termed computational battery dynamics (CBD). This general-purpose framework makes use of the similarity in the equations governing different battery systems, and has resulted in the development of robust models in a relatively short time. Here we review this framework, in the context of applications to the coupled modeling of the thermal and electrochemical behavior of cells, and to the modeling at three different scales, namely pore-level, cell-level and stack-level. The similarity and differences of our approach with other research groups are exemplified. Significant results from each of these advanced applications of modeling are highlighted with emphasis on the insights that can be gained from a first-principles model. In addition, we also demonstrate the usefulness of a combined experimental-modeling approach in describing cells. The models reviewed here are expected to be useful in predicting the behavior of advanced batteries used in electric vehicles (EVs) and hybrid electric vehicles (HEVs).