Project Details
Description
Project Summary
Recently employed intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is a promising
treatment for the wet form of age-related macular degeneration with choroidal neovascularization (CNV) and
diabetic retinopathy. In fact, the anti-VEGF therapy has become a gold standard for these diseases. While the
therapeutic effects are positive, a major drawback is that this treatment must be repeated every four to six weeks.
The repetitive treatment burden on the patients, family members, and clinicians is substantial. Recently, we have
developed a biodegradable microspheres, thermo-responsive hydrogel ocular drug delivery system (DDS).
Biodegradable microspheres are produced using our modified double emulsion technique providing a better
microenvironment for pharmacological agents. The biodegradable thermo-responsive hydrogel is a safe,
effective, and injectable biomaterial that is used to confine the microspheres to a specific delivery site. We have
previously demonstrated a controlled sustained release of anti-VEGF for a period of 6 months with excellent
safety profiles. The overall goal of this proposal is to quantitatively evaluate the safety and efficacy of our
proposed DDS in a non-human primate model and compare to the conventional therapy. Our hypothesis is that
a sustained controlled anti-VEGF release over a prolong period of ~6 months, will be as effective, if not more
effective, as the conventional therapy. The Specific Aim 1 is to determine ocular pharmacokinetics (PK) of
aflibercept released from DDS in a non-human primate (NHP) model. The Specific Aim 2 to determine
biocompatibility of DDS in a NHP model. The Specific Aim 3 is to quantitatively compare the efficacy and
bioactivity of the proposed DDS to the conventional therapy in its ability to suppress angiogenic responses in
CNV model. The Specific Aim 4 is to measure long-term potential side effects, if any, of the proposed DDS and
exposure of anti-VEGF in a rodent model. The Specific Aim 5 is to quantitatively evaluate the drug release
kinetics and bioactivity of the dual-drug release DDS. Widespread clinical use of anti-VEGF necessitates a
practical and effective delivery method to the posterior segment of the eye. We believe that our drug delivery
system will fill this critical clinical need. The knowledge gained in this proposal will bring this technology one step
closer to translation into the clinical practice and will have a significant impact on the current healthcare system.
Status | Finished |
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Effective start/end date | 1/05/19 → 29/02/24 |
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