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.
Highlights
The eye-ball is an organ protected from exogenous substances and external stress by various barriers (Figure 1), therapeutic drugs must be transported across several protective barriers regardless of which administration route is utilized, such as eye-drops, and subconjunctival, sub-tenon’s and intravitreal injection and/or implant.For the treatment of the anterior segment of the eye, usually topical ocular eye-drops are used
Soft contact lens-based drug delivery systems (DDSs) have been investigated by several approaches: (1) Soak and absorption of drug solution [86]; (2) piggyback contact lens combined with a drug plate or drug solution [87]; (3) surface-modification to immobilize drugs on the surface of contact lenses [88]; (4) incorporation of drugs in a colloidal structure dispersed in the lens [89]; (5) ion ligand-containing polymeric hydrogel [90]; and (6) molecularly imprinting of drugs [91,92]
The commercial failure of inserts might be attributed to psychological factors including the reluctance to abandon the traditional droppable formulations, and occasional ejection from the eye observed in the case of Ocusert®
Summary
The eye-ball is an organ protected from exogenous substances and external stress by various barriers (Figure 1), therapeutic drugs must be transported across several protective barriers regardless of which administration route is utilized, such as eye-drops, and subconjunctival, sub-tenon’s and intravitreal injection and/or implant. There is rapidly growing interest in drug delivery systems (DDSs) to the posterior segment of the eye. Compliance is problematic, among patients who have chronic diseases such as glaucoma and refractory chorioretinal diseases, including uveitis, macular edema, neovascular (wet) and atrophic (dry) age-related macular degeneration (AMD), and retinitis pigmentosa (RP) It has been reported nearly 50% of glaucoma patients discontinued all topical ocular hypotensive therapy within six months [5]. AMD: age-related macular degeneration, ARPE-19: human retinal pigment epitheliums cells, BRVO: branch retinal vein occlusion, CMV: cytomegalovirus, CNTF: ciliary neurotrophic factor, CRVO: central retinal vein occlusion, DME: diabetic macular edema, EVA: ethylene-vinyl acetate copolymer, IV: Intravenous, IVT: intravitreal, PLGA: poly(lactide-co-glycolide), PMMA: poly(methyl methacrylate), PVA: poly(vinyl alcohol), RP: retinitis pigmentosa
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