Nanoparticles that do not compete with endogenous ligands - Molecular characterization in vitro, acute safety in canine, and interspecies pharmacokinetics modeling to humans.

ABSTRACT: A vast majority, if not all of the receptor-mediated drug delivery systems utilize nanoparticles that are conjugated to physiological mimic ligands, with testing restricted to in vitro and rodent models. In this report, we present for the first time, a full spectrum characterization of transferrin receptor 1 (TfR1)-targeted polymeric nanoparticles (abbreviated, P2Ns-GA) that do not compete with endogenous transferrin, and serve as a versatile platform for oral drug delivery. Based on endocytosis inhibitors and receptor knockdown, the cellular uptake of P2Ns-GA is clathrin-mediated and dependent on TfR1 expression, but other trafficking mechanisms, particularly those involving caveolae/lipid rafts, can also play a role. The utility of P2Ns-GA in promoting the oral bioavailability of encapsu

SUBMITTER: Zou D 

PROVIDER: S-EPMC8089043 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature