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Anjali Hirani, Yong W Lee, Vijaykumar Sutariya, Yashwant Pathak; Loteprednol Drug Delivery System for Treatment of Choroidal Neovascularization in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5038.
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Age-related macular degeneration is the leading cause of vision loss in adults over 50. The neovascular form is characterized by choroidal neovascularization (CNV); growth of abnormal blood vessels under the retina which can leak blood and fluid and cause deterioration to the macula over time. Current treatments utilize frequent intravitreal injections which can result in retinal detachment and increased ocular pressure. In this study, we investigated a nano sustained drug delivery system for the treatment of choroidal neovascularization present in wet age-related macular degeneration.
The drug delivery system (DDS) was comprised of loteprednol etabonate, poly(ethylene glycol)-ylated (PEGylated) poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs), and a PLGA-PEG-PLGA thermoreversible gel. The loteprednol-loaded NPs were prepared using the nanoprecipitation method. The loteprednol NPs were then incorporated into a 20% (w/v) thermoreversible gel prepared using the cold method. An in vitro dialysis method was employed to measure the release of loteprednol from the DDS over time. Cellular uptake imaging nanoparticles in human retinal pigment epithelial cells (ARPE-19) was studied via confocal microscopy. The effect of the DDS on VEGF secretion was quantified by ELISA method.
Nanoparticle characterization data showed an average particle size of 168.60 ± 23.18 nm, polydispersity index of 0.0142 ± 0.0023 nm, and encapsulation efficiency of 82.6%. In vitro release results demonstrated free loteprednol was completely released within 48 hours; whereas loteprednol was released from the DDS over 10 days. Cellular uptake imaging demonstrate complete uptake of loaded nanoparticles in ARPE-19 cells within 1 hour. Cells treated with 10 μM loteprednol DDS showed a significant reduction of VEGF secretion of 16% as compared to the equivalent treatment of loteprednol alone.
These results suggest that the proposed delivery system for loteprednol could be an effective sustained release treatment for ocular dysfunction.
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