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Jennifer J. Kang Mieler, Christian R. Osswald, Micah J. Guthrie, William F. Mieler; Efficacy Of Dexamethasone Sodium Phosphate Nanospheres Within Thermo-responsive Hydrogel Treatment In A Laser Induced Choroidal Neovascularization Animal Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2267.
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Nanospheres embedded within thermo-responsive hydrogels were used to encapsulate dexamethasone sodium phosphate (DSP). The efficacy of DSP released from the nanosphere-thermo-responsive hydrogel complex was examined in a laser-induced choroidal neovascularization (CNV) rodent model.
DSP was encapsulated in poly(D, lactide-co-glycolide) nanospheres (50:50, Mw 7K-17K) using an oil in water double-emulsion technique. Thermo-responsive hydrogel was synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and crosslinked with polyethylene glycol-diacrylate (PEG-DA) and 5% A-lysine and 15% NtBAAm. DSP-loaded nanospheres were added to the hydrogel solution prior to addition of the initiators. Long-Evans pigmented rats were used to induce laser-induced CNV (5-7 lesions per eye). One hour post-CNV induction, 5 µl of DSP-nanosphere-thermo-responsive hydrogel was given intravitreally. Results were compared to control Group 1 that received an intravitreal injection of DSP solution and Group 2 that received an intravitreal injection of thermo-responsive hydrogel without DSP-loaded nanospheres. Intraocular pressure (IOP), retinal blood flow, electroretinogram (ERG), and CNV areas were monitored weekly for four weeks following CNV-induction. The degree of CNV inhibition was determined by measuring the lesion size using SLO fluorescein images.
DSP released from nanospheres suspended in the hydrogels lasted for ~24 hours. No significant changes in IOP were observed after the intravitreal injections. At four weeks, CNV areas in DSP-nanosphere-hydrogel treated eyes were reduced over 7-fold (0.75±0.77 to 0.10±0.17mm2), Group 1 reduced 3-fold (0.87±0.96 to 0.28±0.42mm2) and Group 2 had no significant change in lesion size (0.71±0.51mm2). Corneal a- and b-wave ERG half-saturation sensitivities (1.203±0.004 and 0.003±.001 cd·s/m2, respectively) were unchanged throughout the four weeks compared to control measurements. Arterial (12.8±1 μL/min) and venous (22.9±3 μL/min) retinal blood flow did not significantly change throughout the four weeks when compared to control measurements.
Continuous release of DSP through nanosphere-hydrogel complex resulted in a significant reduction in CNV lesion size. No detectable adverse side effects were observed. The investigated DSP-loaded nanosphere-thermo-responsive hydrogel system is a promising, relatively non-invasive delivery platform.
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