Generation of a Human Conditionally Immortalized Cell-based Multicellular Spheroidal Blood-Brain Barrier Model for Permeability Evaluation of Macromolecules.

There is an urgent need for the development of brain drug delivery carriers based on middle-sized or macromolecules, to which blood-brain barrier (BBB) models are expected to contribute significantly through evaluation of BBB permeability. As part of efforts to develop such models, we have been working on human conditionally immortalized cell-based multicellular spheroidal BBB models (hiMCS-BBB models), and we herein introduce the model development protocol. Briefly, astrocytes are first seeded in an ultra-low attachment 3D cell culture plate, to make the central core (Day 0).

Human Immortalized Cell-Based Blood-Brain Barrier Spheroid Models Offer an Evaluation Tool for the Brain Penetration Properties of Macromolecules.

Blood-brain barrier (BBB)-permeable middle- or macromolecules (middle/macromolecules) have recently attracted significant attention as new drug delivery carriers into the human brain via receptor-mediated transcytosis (RMT). During the development process of such carriers, it is necessary to thoroughly evaluate their human BBB permeability levels. In such evaluations, our recently established human immortalized cell-based multicellular spheroidal BBB models (hiMCS-BBB models) have shown high potential.

In Vitro-In Vivo Correlation of Blood-Brain Barrier Permeability of Drugs: A Feasibility Study Towards Development of Prediction Methods for Brain Drug Concentration in Humans.

Purpose: In vitro human blood-brain barrier (BBB) models in combination with central nervous system-physiologically based pharmacokinetic (CNS-PBPK) modeling, hereafter referred to as the "BBB/PBPK" method, are expected to contribute to prediction of brain drug concentration profiles in humans. As part of our ongoing effort to develop a BBB/PBPK method, we tried to clarify the relationship of in vivo BBB permeability data to those in vitro obtained from a human immortalized cell-based tri-culture BBB model (hiBBB), which we have recently created.

Methods: The hiBBB models were developed and functionally characterized as previously described.