Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules.

ABSTRACT:

Purpose

Development of therapeutics for retinal disease with improved durability is hampered by inadequate understanding of pharmacokinetic (PK) drivers following intravitreal injection. Previous work shows that hydrodynamic radius is correlated with vitreal half-life over the range of 3 to 7 nm, and that charge and hydrophobicity influence systemic clearance. Better understanding the molecular attributes affecting vitreal elimination half-life enables improved design of therapeutics and enhances clinical translatability.

Methods

Impacts of charge and hydrophobicity on vitreal PK in the rabbit were systematically assessed using antibody and antibody fragment (Fab) variant series, including ranibizumab, altered through amino acid changes in hypervariable regions of the light

SUBMITTER: Crowell SR 

PROVIDER: S-EPMC6827426 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature