Purchase this article with an account.
T. L. Lowe, G. P. Misra, D. Daley, H. Imai, R. Disantis, T. W. Gardner; Tailored Nanogels for Controlled Delivery of Therepeutics across Ocular Biological Barriers. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2425.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Many ocular therapeutics lack efficacy because of less efficient delivery due to ocular biological barriers. The present study aims at developing degradable nanogels with enhanced permeability for controlled release of therapeutics to the back of the eye.
Nanogels, consisted of N-isopropylacrylamide and 2-hydroxyl methacrylate-lactide-dextran macromer, were synthesized in aqueous medium using UV photopolymerization under stirring. The size and morphology of the nanogels were studied by dynamic light scattering (DLS) and atomic force microscopy (AFM). Fluorescent-labeled insulin was loaded the nanogels during the synthesis process and released from the nanogels at solute concentration 2 mg/mL in phosphate buffered saline (PBS, pH 7.4) at 37 °C. Cytotoxicity of the nanogels to R28 and ARPE-19 retinal cells, and human brain microvessel endothelial cells (HBMVECs) was studied by a MTT cell viability assay. Permeability of the 100 µg/mL nanogels across the ARPE-19 and HBMVE monolayers was measured. Fluorescent-labeled nanogels were injected intravitreally and intravenously into Sprague-Dawley rats and their distribution in the retina, vitreous, cornea, and lens was assessed 1day later.
DLS and AFM data revealed that the size of the nanogels was around 70-90 nm. Nanogles released FITC-labeled insulin for 2 days in PBS at 37 °C. The nanogels were not cytotoxic to the R28 and ARPE-19 cells at concentration up to 1 mg/mL for at least one week. They were 10 and 5 folds more permeable than 4kDa dextran across the ARPE-19 and the HBMVEC monolayers, respectively. The fluorescent-labeled nanogels were detected in the retina but not in the cornea, lens, and vitreous after intravenous injection. In contrast, intravitreal injection indicated the presence of nanogels in the cornea and vitreous but not in the lens, and retina.
The developed degradable nanogels are non-toxic and have potential to cross ocular biological barriers and deliver drugs to the retina.
This PDF is available to Subscribers Only