Intravitreal drug delivery in retinal disease: are we out of our depth?

Expert Opin Drug Deliv. 2014 Oct;11(10):1575-90. doi: 10.1517/17425247.2014.927864. Epub 2014 Jun 14.

Abstract

Introduction: With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise.

Areas covered: We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally.

Expert opinion: Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully; however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.

Keywords: drug delivery; intravitreal delivery; nanoparticles; retina; retinal barriers; retinal models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Retinal Barrier
  • Drug Delivery Systems*
  • Humans
  • Intravitreal Injections
  • Ophthalmic Solutions / administration & dosage*
  • Pharmaceutical Preparations / administration & dosage*
  • Retinal Diseases / drug therapy*

Substances

  • Ophthalmic Solutions
  • Pharmaceutical Preparations