Purpose: Age-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use.Methods: This provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers.Results: Polymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed.Conclusion: The use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.

The vitreous humor is a fragile, transparent hydrogel situated between the lens and the retina, occupying 80% of the eye's volume. Due to its viscoelastic behavior, the vitreous serves as a mechanical damper for the eye, absorbing impacts, and protecting the lens and retina. The vitreous liquefies with age, which compromises its function as a shock absorber and causes complications including retinal detachment, macular holes, and vitreous hemorrhage. Studies on the viscoelastic properties of the vitreous have been limited. Rheological testing of the vitreous has commonly been done on non-primate mammalian species. Human vitreous rheological properties have been previously reported; however, various measurement techniques were used, resulting in data that differed by orders of magnitude. Shear rheometry is commonly used to characterize soft tissues and hydrogels such as the vitreous humor. However, no human vitreous rheological data have been reported using this technique, preventing direct comparison to other published work. Additionally, no age-related changes in the mechanical properties of the human vitreous humor have been reported. Human vitreous samples (n = 39, aged 62 ± 15 years) were tested using a shear rheometer. Small amplitude oscillatory shear and creep experiments were performed. The linear viscoelastic region of the human vitreous was found to be below 1% strain. The solid phase of the old human vitreous was found to be stiffer than the young human vitreous and the porcine vitreous. The stiffness of the human vitreous gel also appeared to be positively correlated with age. Vitreous dehydration due to a decrease in hyaluronic acid concentration with age was proposed to cause the stiffening of the solid phase of the vitreous gel. Vitreous liquefaction, therefore, might be characterized as a simultaneous increase in liquid volume and localized stiffening of the vitreous gel. The phase separation of the vitreous humor with age has been hypothesized as the cause of many vitreous-related complications. This study provides viscoelastic properties and age-related changes of the human vitreous humor, which will aid in the design of biomimetic vitreous substitutes, enhancement in analyzing intravitreal transport of therapeutics, and understanding the pathological conditions of the vitreous humor.

The vitreous humor occupies two thirds of the volume of the eye and is the major component behind the lens. The human vitreous is a gelatinous substance predominantly composed of water (98-99%). Its functions include holding the retina in place and circulating metabolites throughout the eye. The vitreous liquifies with age, facilitating posterior vitreous detachment, which can lead to retinal tears, intravitreal hemorrhage or retinal detachment. Vitreous substitutes are needed to tamponade the retina or during vitrectomies for treatment of retinal detachments. Gases, perfluorocarbon liquids and silicone or fluorosilicone oils are currently used as vitreous substitutes; however, none of these substitutes can be used long term due to the short retention time of the gaseous substitutes, cell toxicity or other complications, such as glaucoma or cataracts. Vitreous substitutes, both experimental and clinical, will be reviewed, along with promising experimental artificial vitreous; polymeric hydrogels.

Purpose. An in situ forming hydrogel was evaluated as a potential vitreous substitute in rabbits. methods. The hydrogel used a disulfide cross-linker that was then reduced to produce an injectable thiol-containing polymer solution. The disulfide cross-links reformed by air oxidation of the thiols and produced a stable hydrogel once inside the eye. The polymer was clear, autoclavable, and could be stored easily in the presence of nitrogen gas. Capillary rheometry was used to measure the viscoelastic properties of the hydrogels and the porcine vitreous. Fourteen black rabbits underwent a pars plana, 25-gauge, three-port vitrectomy by a single surgeon with injection of a vitreous substitute. results. The refractive indices of the hydrogels were measured by refractometry and were shown to be close to 1.33, and the 2% hydrogel matched the mechanical properties of the natural vitreous humor. The reduced polymeric hydrogel was easily injectable through a small-gauge needle into the vitreous cavity and did not show any fragmentation. The material underwent gelation within the eye, remained optically clear, and appeared well tolerated clinically. Slit lamp examination, dilated fundus examination, and electroretinograms showed no evidence of vitritis, uveitis, or endophthalmitis after 1 week. Histopathologic evaluation did not reveal any overt toxicity or gross morphologic changes in the retina. conclusions. The fact that this process of in situ gelation gives rise to hydrogels that are biocompatible and physically and optically similar to the natural vitreous suggests its suitability as a permanent vitreous substitute. Hydrogel candidates will be further studied to evaluate long-term biocompatibility and degradation in vivo.

Reactive oxidative species (ROS) are the primary mediator of angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF) in the development of wet age-related macular degeneration (AMD). However, the current treatment of AMD currently relies on monthly intravitreal injection of anti-angiogenic therapeutics to inhibit new choroidal angiogenesis. However, repeated injections have been associated with side-effects, are costly, and may lower patient compliance. Moreover, the intraocular oxidative stress-dependent angiogenesis is not alleviated by current treatments, which limits the overall efficacy of the treatment strategy. Recently, nanoparticle-based devices present potential in sustained delivery of angiogenesis inhibitors and excellent capability of scavenging reactive oxygen species (ROS). Nevertheless, limited efforts have been dedicated to the treatment of oxidative stress-related diseases via a combined anti-angiogenesis and anti-oxidization pathway. For this purpose, we developed anti-angiogenetic protein-loaded polydopamine (PDA) nanoparticles for the enhanced treatment of AMD. Remarkably, the PDA nanoparticles could efficiently scavenge ROS to reduce the expression of angiogenic agents. In parallel, the particles were able to controllably release loaded anti-angiogenic drugs in response to oxidative stress.