A Controlled Release System for Long-Acting Intravitreal Delivery of Small Molecules.

ABSTRACT:

Purpose

The short half lives of small molecules in the vitreous requires frequent repeated intravitreal injections that are impractical for treatment of chronic eye diseases. We sought to develop a method for increasing the intravitreal half-life of small-molecule drugs.

Methods

We adapted a technology for controlled release of drugs from macromolecular carriers for use as a long-acting intravitreal delivery system for small molecules. As a prototype, a small molecule complement factor D inhibitor with an intravitreal half-life of 7 hours was covalently attached to a 4-arm PEG_40kDa by a self-cleaving β-eliminative linker with a cleavage half-life of approximately 1 week.

Results

After intravitreal injection in rabbits, the drug was slowly released in the vi

SUBMITTER: Machinaga N 

PROVIDER: S-EPMC6114027 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature