Stability and ocular biodistribution of topically administered PLGA nanoparticles

The spatiotemporal distribution profile of polymeric nanoparticles (NPs) in the eye is important as it will determine their effectiveness as topical ocular drug delivery systems for specific eye diseases. Physical stability of the nanoparticles in an ophthalmic formulation and thermal stability of the entrapped drug are critical as well to the applicability of polymeric nanoparticles as drug delivery to the eye. To investigate these characteristics, Cy5-labeled, poly(lactic-co-glycolic acid) (PLGA) NPs (ζ-potential: -14.1±1.5 mV, size: 241.7±0.6 nm) and lutein-loaded PLGA NPs (ζ-potential: -6.7±0.3 mV, size: 210.6±3.3 nm) were synthesized, and their stability and biodistribution were assessed. Lutein-loaded NPs were stable at 4°C without significant changes in size and morphology, without significant lutein degradation, and 26% release after 5 weeks in suspension. In contrast, lutein-loaded NPs stored at 25°C and 37°C experienced significant changes in size, likely due to aggregation and surfactant dissociation; these NPs showed signs of bulk degradation based on transmission electron microscopy (TEM), and had significant lutein degradation and over 40% release after 5 weeks. Lutein loaded in NPs 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 NP therapeutics in vivo, Cy5-labled NPs were applied topically to the eyes of rats and incubated for 15 min, 30 min, or 60 min. 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 at 1 h compared to 30 min, indicated rapid elimination of NPs from the eye.