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Rami Elhayek, Rami Elhayek, Peter Jarrett, Amar Sawhney, Sarah Guedez; Sustained release of ovalbumin and IgG from hydrogel depots as surrogate proteins for intravitreal injection. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1095.
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To evaluate the sustained release of ovalbumin (OVA; 45000 g/mol) and rabbit IgG (rIgG; 150000 g/mol) from preformed hydrogel depots with variable degradation times.
: Fine particles of OVA and IgG were formulated with a selection of PEG hydrogels and were cured, dried and cut to form degradable (a, b, c, d) and non-degradable (e) hydrogel depots. The depots were examined in vitro for sustained release under accelerated conditions. Prior to testing, acceleration rate was calculated using degradation profiles of each hydrogel, absent of OVA and IgG, to compare the relative degradation rate between accelerated and real-time conditions, tris buffer saline (TBS) pH8.5 and phosphate buffer saline (PBS) pH7.4, respectively. Acceleration factor was determined to be 16x in TBS compared to PBS. Accelerated OVA and IgG in vitro release was conducted to determine release profiles as a function of the hydrogel degradation over time. Concentration of OVA and rIgG were determined by HPLC.
Release profiles of OVA and rIgG shown in Figure 1 and 2 show the effect of hydrogel degradation time on sustained release of OVA and rIgG. Slow degrading hydrogels release OVA and rIgG over a longer time period than faster degrading hydrogels. Comparison of OVA and rIgG release using the same hydrogels indicate that rIgG is released slower than OVA due the difference in size and molecular weight. In both cases, hydrogels made using non-degradable SGA linkages used as controls reach a maximum release after diffusion of surface and free particles.
Monoclonal antibody fragments and fusion proteins have been designed to inhibit vascular endothelial growth factors (VEGF) for treatment of posterior segment diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME). Frequent anti-VEGF intravitreal injections have shown to manage the progression of these diseases to prevent further vision loss and in some cases, gain visual acuity. However, frequent intravitreal injections can increase the risk of infection, retinal detachment, and/or hemorrhage. The ability to tailor the release of OVA and rIgG from hydrogel depots for sustained delivery of proteins could provide a technology platform for use with anti-VEGFs to reduce the number of yearly intravitreal injections and potentially reduce the risk of side effects.
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