Polyesters with controlled topologies for probing transcytosis at the gut-blood barrier
CO-PI: Dhaval Shah, University at Buffalo
In pursuit of clinical translation of polymer nanoparticles, this proposal aims to synthesize polyesters with controlled topologies for probing transcytosis at the gut-blood barrier and develop quantitative tools in the form of mathematical systems physiologically based pharmacokinetic (PBPK) models. Towards this goal, a series of in vitro, in vivo, and in silico investigations in translationally relevant preclinical species are proposed to obtain unprecedented quantitative insight into the processes responsible for absorption, distribution, metabolism, and elimination (ADME) of drug-laden polymer nanoparticles. In addition, all the preclinical data will be mathematically integrated simultaneously using a novel bottom-up systems PBPK model, which can serve as a quantitative tool for preclinical-to-clinical translation of orally administered drug-laden polymer nanoparticles.
- D. Zou, M. Arora, R. Ganugula, M. Kumar, E. M. Scott, D. Shah, M. N. V. Ravi Kumar. Nanoparticles that do not compete with endogenous ligands–molecular characterization in vitro, acute safety in canine, and interspecies pharmacokinetics modeling to humans. J. Control. Release 332, 64-73, 2021