Recent advances in slow and sustained drug release for retina drug delivery

ABSTRACT

Introduction: Striking recent advance has occurred in the field of medical retina, greatly because intraocular drugs have been developed, enhancing their clinical efficacy while avoiding systemic side-effects. However, the burden of repeated intraocular administration makes limits the optimal efficacy of treatments, prompting the development of new drugs with prolonged half-life or of sustained drug delivery systems.

Area covered: In this review, we describe the various drugs and drug delivery systems that have reached the clinical stage and those that are in clinical development and we discuss the limitations to clinical translation.

Expert opinion: Substantial fundamental work is still required to build guidelines on optimal animal models for ocular pharmacokinetics and safety studies depending on the target disease site and the on the type of therapeutic compounds. The effects of a drug administered as a bolus at high concentration in the vitreous might differ from those resulting from the sustained release of a lower concentration, and no delivery platform can be simply adapted to any drug. For the treatment of retinal diseases, development of therapeutic compounds should integrate from its early conception, the combination of an active drug with a specific drug delivery system, administered by a specific route.

KEYWORDS:

• Ocular pharmacokinetics
• drug delivery
• retina
• therapeutic proteins
• vitreous implants
• polymers
• nanosystems

Article highlights

• Drug delivery remains a major challenge in the treatment of retinal diseases

• Degradable and non-degradable implants for the sustained and local release of glucocorticoids have been approved

• Bolus of proteins neutralizing VEGF family members allow the maintenance of clinical benefit for 1 to 3 months

• New reservoirs and polymeric dispersed systems are in development for intravitreous slow release of drugs and proteins

• Few drug delivery systems cross the clinical stage due to insufficient multi-disciplinary development

• Fundamental work is still required to build guidelines for toxicity and models for ocular pharmacokinetic studies.

Declaration of interest

F Behar-Cohen is the founder of Eyevensys and has patents on the technology developed by Eyevensys which includes the electroporation of plasmids in the ciliary muscle for the production of therapeutic proteins. F Behar-Cohen has consulted for Bayer, Novartis, Roche, Boehringer Ingelheim, Thrombogenics, Allergan. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.