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Trivedi Ruchit, Puneet Tyagi, Sunil Vooturi, Uday Kompella; Deslorelin and transferrin mono- and dual- functionalized nanomicelles for drug delivery to the anterior segment of the eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3203.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether encapsulation in novel micelles enhances delivery of hydrophobic molecules to the anterior segment of the eye after topical administration.
Deslorelin and transferrin were conjugated with PLGA polymer using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide. Conjugation was confirmed using infrared spectroscopy (FTIR) and MALDI-TOF mass spectrometry. Micelles were formed by the addition of conjugates in dichloromethane to water, and characterized for appearance, size, zeta potential, and CMC. Uptake of Nile red (NR) and pazopanib (anti-angiogenic drug) loaded micelles following topical administration was evaluated in an ex-vivo bovine eye model at 5 and 60 minutes post administration using fluorescence spectroscopy for NR and mass spectroscopy for pazopanib.
FTIR and MALDI-TOF confirmed conjugate formation. Sizes were 89.0, 74.3, and 59.4 nm, CMCs were 2.5, 100, and 2.5µg/ml, and zeta potentials were 1.0, 21.5, and 11.5 mV for deslorelin-PLGA, transferrin-PLGA, and mixed micelles, respectively. Pink colored, uniform appearance indicated NR loading in micelles. Pazopanib loading was 57, 83, and 70 µg/mg micelles, while NR loading was 5, 6, and 5 µg/mg micelles for deslorelin-PLGA, transferrin-PLGA, and mixed micelles, respectively. NR uptake in epithelium was 0.2, 16.1, 14.4, and 19.3%, at 5 minutes and 0.2, 20.8, 20.3, and 24.9 % at 60 minutes for plain NR, deslorelin-PLGA, transferrin-PLGA, and mixed micelles, respectively. Addition of excess deslorelin and transferrin reduced epithelium uptake to 0.31, 10.1, 9.49, and 11.77%, at 5 minutes and 0.25, 13.53, 14.61, and 15.01% at 60 minutes for plain NR, deslorelin-PLGA, transferrin-PLGA, and mixed micelles respectively. Pazopanib uptake in epithelium was 0.4, 14.6, 11.9, and 15.8 % at 5 minutes and 1, 19, 14.9, and 18 % at 60 minutes for plain pazopanib, deslorelin-PLGA, transferrin-PLGA, and mixed micelles, respectively. Stroma showed ≤ 1% uptake for micelles and ≤ 0.03% for plain drug suspension. Endothelium and aqueous humor uptake was negligible for both NR and pazopanib. Micelles increased corneal epithelial delivery by 80-120 fold for Nile red and by 15-39 fold for pazopanib.
Functionalized micelles are promising delivery systems for the delivery of poorly soluble hydrophobic drugs to the anterior segment of the eye.
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