Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor.

ABSTRACT: We develop and analyze mathematical models for receptor-mediated transcytosis of monoclonal antibodies (MAb) targeting the transferrin receptor (TfR) or the insulin receptor (IR), which are expressed at the blood-brain barrier (BBB). The mass-action kinetic model for both the TfR and IR antibodies were solved numerically to generate predictions for the concentrations of all species in all compartments considered. Using these models, we estimated the rates of MAb endocytosis into brain capillary endothelium, which forms the BBB in vivo, the rates of MAb exocytosis from the intra-endothelial compartment into brain extracellular space, and the rates of receptor recycling from the endothelial space back to the luminal endothelial plasma membrane. Our analysis highlights the optimal rates of MA

SUBMITTER: Pardridge WM 

PROVIDER: S-EPMC8226686 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature