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.
Highlights
Abbreviations Analysis of Variance (ANOVA) Analysis of variance AVMA American Veterinary Medical Association dynamic light scattering (DLS) Dynamic light scattering Institution Animal Care and Use Committee (IACUC) Institutional Animal Care and Use Committee LSU A&M Louisiana State University and A&M NP Nanoparticles poly(lactic-co-glycolic acid) (PLGA) Poly(lactic-co-glycolic acid) Polyvinyl Alcohol (PVA) Polyvinyl alcohol region of interest (ROI) Region of interest transmission electron microscopy (TEM) Transmission electron microscopy
The average diameter, polydispersity index (PDI), and ζ-potential of Cy5 and lutein-loaded nanoparticles were measured by Dynamic Light Scattering (DLS) immediately after resuspension (Table 1)
TEM imaging revealed spherical and well-dispersed lutein-loaded and Cy-5 labeled particles in the 200 nm size range in support of the DLS results
Summary
Abbreviations ANOVA Analysis of variance AVMA American Veterinary Medical Association DLS Dynamic light scattering IACUC Institutional Animal Care and Use Committee LSU A&M Louisiana State University and A&M NP Nanoparticles PLGA Poly(lactic-co-glycolic acid) PVA Polyvinyl alcohol ROI Region of interest TEM Transmission electron microscopy. Various treatment methods have been used to deliver pharmaceuticals to the posterior of the eye, including topical, systemic and intravitreal routes. Nanodelivery systems are a pivotal tool to enhance current disease therapies by improving topical passage of large hydrophobic drugs, increasing drug contact time with the target tissue, and improving targeted delivery of drugs to specific ocular tissues[8]. Intravitreal injections are preferred when treating posterior eye diseases due to quick and direct tissue targeting, repeated injections lead to an increased incidence of complications, such as endophthalmitis, retinal detachment, and intraocular hemorrhag[10]. Resistance to photo- and thermal-degradation, release kinetics, and biodistribution of nanoparticle-based lutein therapeutics in the eye are important considerations to optimize treatment effectiveness. We assessed temperature-dependent physical stability of PLGA nanoparticles, thermal stability, photostability and release of lutein from PLGA nanoparticles, and time-dependent ocular biodistribution of topically applied Cy5-labeled PLGA nanoparticles
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