Polymeric Nanoparticles as an Antioxidant Delivery System for Age-Related Eye Disease

Advantages of polymeric nanoparticles as ocular drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. A review was conducted to serve as a guide to optimizing polymeric nanoparticle delivery systems for ocular drug delivery by discussing the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications. Spatiotemporal distribution of polymeric nanoparticles in the eye as well as the physical stability of the nanoparticles in an ophthalmic formulation and thermal stability of the entrapped drug are critical regarding applicability of polymeric nanoparticles for drug delivery in the eye. To investigate these characteristics, Cy5-labeled, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (z-potential: -14.1±1.5 mV, size: 241.7±0.6 nm) and lutein-loaded PLGA nanoparticles (z-potential: -6.7±0.3 mV, size: 210.6±3.3 nm) were synthesized, and their stability and biodistribution were assessed. Lutein-loaded nanoparticles were stable at 4°C without significant changes in size and morphology, without significant lutein degradation, and 26% was released after 5 weeks in suspension. In contrast, lutein-loaded nanoparticles stored at 25°C and 37°C experienced significant changes in size, likely due to aggregation and surfactant dissociation; these nanoparticles showed signs of bulk degradation based on TEM, and had significant lutein degradation and over 40% release after 5 weeks. Lutein loaded in nanoparticles was more resistant to photodegradation compared to a free lutein solution when exposed to UV for 6 h, degrading 5 times slower than free lutein. To test the performance of nanoparticle therapeutics in vivo, Cy5-labled nanoparticles were applied topically to the eyes of rats and incubated for 15 min, 30 min, or 60 min in vivo. Exterior eye tissues including the cornea, episcleral tissue, and sclera showed the highest fluorescence intensity in animals that received fluorescent nanoparticles, while the choroid was the only inner eye tissue that was significantly higher in a treatment group compared to the control group. Additionally, decreases of fluorescence in all exterior eye tissues and the choroid between 30 min and 1 h indicated rapid elimination of nanoparticles from the eye. Antioxidant therapies are of interest in the prevention and management of senile cataracts, however the delivery of antioxidants to the lens is complicated by anatomical barriers and lack of direct blood supply. Polymeric nanoparticles are a potential solution, as they can potentially penetrate the eye and carry otherwise unstable antioxidants such as lutein to targets within the eye. In this study, we investigated the ability of topically administered, lutein-loaded nanoparticles for attenuating the development of selenite-induced cataracts in rats. To enhance the corneal retention time and reduce elimination by lacrimal fluids, nanoparticles were embedded in a thermosensitive hydrogel which solidifies upon contact with the cornea. Among several nanoparticle formulations tested, animals treated with lutein-loaded PLGA nanoparticles at a lutein concentration of 1,278 µg/mL showed the greatest decrease in selenite-induced cataract severity compared other treatment groups and untreated animals. Future tests are warranted in larger animal models to support the hypothesis that topical application of lutein-loaded polymeric nanoparticles is an effective cataract prevention therapy

Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy

Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications

Stability and ocular biodistribution of topically administered PLGA nanoparticles

Abstract Polymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye

Biodistribution of orally administered poly(lactic-co-glycolic) acid nanoparticles for 7 days followed by 21 day recovery in F344 rats

© 2016 Elsevier B.V. The aim of this research was to assess biodistribution of orally administered poly(lactide-co-glycolide) acid nanoparticles (PLGA NPs) in rats and investigate the excretion of PLGA nanoparticles after administration has ended. The experiment was divided into 2 phases. In phase I, F344 rats were orally administered fluorescently tagged PLGA nanoparticles daily (3 mg/day) for 7 days, followed by a mass balance analysis which was performed on tissues of interest to determine NP biodistribution. In phase II, after 7 days of oral exposure, rats were no longer administered PLGA NPs, and amount of NPs excreted was measured each week for 3 weeks. At day seven, the last day of the nanoparticle exposure period, over half of the daily administered PLGA NPs were excreted. Among the nanoparticles recovered from the tissues, the majority was recovered in the intestines (23.4% daily dose), followed by the liver (11.4% daily dose), kidney (5.5% daily dose), spleen (2.5% daily dose), lung (2.0% daily dose), brain (1.0% daily dose), plasma (0.7% daily dose), and heart (0.2% daily dose), respectively. During phase II, the amount of NPs in the feces declined from the maximum excretion on day 7 (58.3% daily dose) to the minimum value on day 28 (6.7% daily dose), 3 weeks after NP administration ended. Little change in nanoparticle excretion was observed between day 21 and day 28, indicating the baseline had been reached. The findings are significant for understanding biodistribution and excretion of orally administered PLGA NPs and are relevant to their application in food, agriculture, and medicine

Toxicity and biouptake of lead and arsenic by Daphnia pulex

Cataracts are responsible for half of the world blindness, surgery being the only viable treatment. Lutein, a naturally occurring carotenoid in the eye, has the potential to reduce cataract progression by protecting the eye from photo-oxidative stress. To restore the eye\u27s natural line of defense against photo-oxidative stress, a formulation was developed using zein and poly(lactic-co-glycolic acid) nanoparticles (NPs) embedded in an optimized bioadhesive thermosensitive gel for the delivery of lutein via topical application. Cataracts were induced in Crl:WI rats via selenite injection at 13 days post-partum, followed by 7 days of treatment with free lutein or lutein-loaded NPs administered orally or topically. Cataract severity was significantly reduced in rats treated with topical applications of lutein-loaded NPs compared to the positive control, while no significant differences were observed in rats treated with other lutein formulations including oral and topically applied free lutein