Development of drug-delivery systems to the posterior segments of the eye

Abstract

In general, vitreoretinal diseases are refractory to both topical and systemic pharmacological approaches because of the anatomical specificity of the eye. That is, the cornea, sclera, tear turnover, frontward current of aqueous humor, blood–aqueous barrier and blood–retinal barrier strictly limit penetration and diffusion of drugs into the chorioretinal tissue. However, recent advances in intraocular drug delivery systems have enabled some compounds to be targeted spatiotemporally into the posterior segments of the eye. Clinically successful or promising cases involve an intraocular nonbiodegradable implant containing ganciclovir for the treatment of cytomegalovirus retinitis, an intraocular biodegradable implant of dexamethasone for the treatment of macular edema, intravitreal or sub-Tenon’s injection of triamcinolone acetonide for the treatment of macular edema or exudative age-related macular degeneration (AMD) and a photodynamic therapy with verteporfin, a photosensitizer, for the treatment of exudative AMD. More recently, a variety of pharmacological challenges to treat exudative AMD are proceeding into clinical trials, as soon as antivascular endothelial growth factor therapies have been proved to be effective by repeated intravitreal injections. In the near future, drug delivery systems will be required to improve the current efficacy and pharmacokinetics of potent antiangiogenic agents or other types of drug. Strategies to enhance the efficacy of available drugs involve: combination therapy (e.g., photodynamic therapy and steroid, photodynamic therapy and antivascular endothelial growth factor therapy), controlled release of drug with biodegradable or nonbiodegradable implants and drug targeting by the modification of a systemically administered drug.

Keywords::

• age-related macular degeneration
• controlled release
• drug targeting
• intraocular drug delivery systems
• retina