Article
Slow-release therapy for AMD, DME on horizon
Slow release of surrogate proteins over several months has been demonstrated in vitro from injectable hydrogel depots. This technology could help create long-term, sustained-release treatments of anti-vascular endothelial growth factor drugs.
Take-Home
Slow release of surrogate proteins over several months has been demonstrated in vitro from injectable hydrogel depots. This technology could help create long-term, sustained-release treatments of anti-vascular endothelial growth factor drugs.
Release profiles of ovalbumin (OVA) and rabbit immunoglobulin G (rIgG) show the effect of hydrogel degradation time on sustained release of OVA and rIgG. A comparison of OVA and rIgG release using the same hydrogels indicates that rIgG is released more slowly than OVA due to the difference in molecular size. (Figures courtesy of Rami El-Hayek, PhD)
Seattle-The slow release of protein-based drugs presents a difficult formulation challenge due to the fragile nature of their molecular structure, such as vascular endothelial growth factor (VEGF) inhibitors.
Studying the release rates of surrogate proteins or antibodies-such as ovalbumin (OVA) and rabbit immunoglobulin G (rIgG)-from hydrogel depots may signify viability of the sustained-release technology for long-term, anti-VEGF therapies to treat retinal diseases, such as age-related macular degeneration (AMD) and diabetic macular edema (DME), explained Rami El-Hayek, PhD, at the annual meeting of the Association for Research in Vision and Ophthalmology.
Though frequent intravitreal injections of anti-VEGF drugs can manage progression of these diseases to prevent vision loss-and, in some cases, increase visual acuity levels-frequent intravitreal injections are associated with increased risks of infection, retinal detachments, and hemorrhages, and carry a substantial financial and time burden for patients. Sustaining the delivery of such drugs over extended periods, resulting in fewer injections and lower risks to patients, could be a breakthrough therapy in ophthalmology and would be easily applied in other areas where high-molecular, weight-active pharmaceutical ingredients need to be delivered over months versus days or weeks.
Injectable hydrogel depots
Dr. El-HayekDr. El-Hayek and his colleagues at Ocular Therapeutix conducted a study to evaluate the sustained release of OVA and rIgG in vitro from pre-formed injectable hydrogel depots with variable degradation times. Fine particles of the two substances were formulated with hydrolytically degradable synthetic poly(ethylene glycol) hydrogels to form degradable depots.
The depots were examined in vitro for sustained release under accelerated conditions. The concentrations of OVA and rIgG were determined by high-performance liquid chromatography. A comparison of the release of OVA and rIgG using the same hydrogels showed that rIgG was released more slowly than OVA because of differences in the sizes and molecular weight of the molecules. It should be noted that OVA and rIgG released over 3 to 6 months still preserved their structure and stability and did not aggregate.
“Rapidly or slowly degrading hydrogel formulations can be tailored for different drug-release rates and durations required by specific therapies covering a range of therapy release times extending to 6 months and even longer,” Dr. El-Hayek said.
In this study, hydrogels made using non-degradable linkages used as controls reach maximal release after diffusion of surface and free particles, but still held the OVA and rIgG particles over a long duration, thus demonstrating that the hydrogel degradation regulated release.
More convenient therapies
This proprietary technology seems to be a major step toward more convenient therapies for posterior segment diseases. The ability to individualize the release of OVA and rIgG from hydrogel depots for sustained delivery of proteins could provide a technology platform that can be used with anti-VEGF therapies to reduce the number of yearly intravitreal injections and potentially reduce the risk of side effects, Dr. El-Hayek concluded.
Rami El-Hayek, PhD
Dr. El-Hayek is an employee of Ocular Therapeutix.
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