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Uday B. Kompella, Arun K. Upadhyay; Trasferrin-functionalized PLGA Nanopartilces Sustain Diclofenac Delivery to Choroid-RPE. Invest. Ophthalmol. Vis. Sci. 2012;53(14):451.
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© ARVO (1962-2015); The Authors (2016-present)
To develop topically applied transferrin-functionalized, biodegradable, polymeric nanoparticles to enhance and sustain diclofenac delivery for treating choroidal neovascularization.
Diclofenac and Nile red loaded poly(lactide-co-glycolide) (PLGA) nanoparticles were prepared using double emulsion and solvent evaporation method. Nanoparticles were chemically conjugated to amino groups on transferrin through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDAC) activation of carboxyl group present on PLGA. In vitro release of diclofenac from nanoparticles was assessed under sink condition at 37 °C. Diclofenac and Nile red were quantified using UV absorbance at 276 nm and 520 nm (Nile red absorbance maxima in 1:1 acetonitrile:water mixture), respectively. In vitro uptake of nanoparticles was evaluated in ARPE-19 and MDCK1 cells. Briefly, cells at 80 % confluence were incubated with 100 μg/ml nanoparticles in serum free medium for 5 min, the medium was removed, cell monolayer was washed - 2 times each with physiological PBS (7.4) and acidic PBS (pH 5.2), cells were lysed using 2% Triton X-100 and Nile red was extracted from particles using dichloromethane, and Nile red content was estimated using UV absorbance at 554 nm (absorption maxima in dichloromethane). Following single topical application of two drops of 10 μl nanoparticle suspension (0.35% w/v diclofenac acid) NP or equivalent dose of plain diclofenac sodium solution in Brown Norway rats, drug delivery was determined by LC-MS method. Nanoparticles were assessed for size using Malvern nanosizer.
Transferrin-functionalized diclofenac PLGA nanoparticles had a mean diameter of 230-260 nm and a negative zeta-potential. Drug release was sustained during the one week in vitro study. ARPE-19 and MDCK1 cells showed 3-4 times higher uptake of transferrin-functionalized diclofenac-PLGA nanoparticles when compared to non-functionalized nanoparticles. At the end of one week following single dose, diclofenac levels in rat choroid-RPE were significantly higher with functionalized PLGA nanoparticles when compared to non-functionalized nanoparticles and plain drug solution.
Transferrin functionalization enhances cellular delivery of nanoparticles and allows sustained and enhanced delivery of diclofenac to choroid-RPE for one week following eye drop administration.
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