Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

Abstract:Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

In general, it is difficult to achieve effective levels of drugs in the vitreous and the retina via topical and/or systemic administration. Intraocular drug delivery systems that achieve longer duration of pharmacological effect with lower administration frequency are urgently needed. Intraocular sustained drug release via implantable devices or injectable particles has been investigated for the treatment of various vitreoretinal disorders. Several non-biodegradable implants are available in clinical practice or in the late developmental phase: Vitrasert (ganciclovir intravitreal implant) for cytomegalovirus retinitis, Retisert (fluocinolone acetonide intravitreal implant) for non-infectious uveitis, Iluvien (fluocinolone acetonide intravitreal implant) for diabetic macular oedema, and NT-501 (a polymer implant containing human retinal epithelial cells genetically modified to secrete ciliary neurotrophic factor) for non-neovascular (dry) age-related macular degeneration and/or retinitis pigmentosa. Many biodegradable formulations, including different shapes of rods, nail-like plugs, discs, or micro- or nanoparticles, have also been investigated, but are not available as yet for the treatment of vitreoretinal disorders. The most developed biodegradable device, Ozurdex (dexamethasone intravitreal implant), is approved as first-line therapy for the treatment of macular oedema following branch retinal vein occlusion or central retinal vein occlusion. In this article, we review the progress of major biodegradable drug delivery systems currently in clinical trials or in experimental stages for the treatment of vitreoretinal disorders.

In both rat strains, P-gp operates in the blood-ocular barriers, and the impact of P-gp on BRB permeability to quinidine and verapamil is lower than that on BBB permeability.