Quantitative measurement of the target-mediated internalization kinetics of biopharmaceuticals.

ABSTRACT:

Purpose

Measurement of internalization of biopharmaceuticals targeting cell surface proteins can greatly facilitate drug development. The objective of this study was to develop a reliable method for determination of internalization rate constant (kint) and to demonstrate its utility.

Methods

This method utilized confocal imaging to record the internalization kinetics of fluorescence-tagged biopharmaceuticals in live-cells and a quantitative image-analysis algorithm for kint determination. Kint was incorporated into a pharmacokinetic-pharmacodynamic (PK-PD) model for simulation of the drug PK profiles, target occupancy and the displacement of endogenous ligand.

Results

The method was highly sensitive, allowing kint determination in cells expressing as low as 5,000 rece

SUBMITTER: Vainshtein I 

PROVIDER: S-EPMC4284384 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature