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Sustained Ocular Drug Delivery System for Anti-VEGF Agents

抗 VEGF 药物持续眼部给药系统

基本信息

批准号：
10363699
负责人：
JENNIFER J Kang-Mieler
金额：
$ 2.5万
依托单位：
ILLINOIS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10363699
关键词：
Age related macular degeneration Animals Aqueous Humor Biocompatible Materials Biodegradable microsphere Blood Vessels Blood flow Bolus Infusion Cataract Choroidal Neovascularization Clinical Clinical Research Data Dexamethasone Diabetic Retinopathy Disease Drug Delivery Systems Drug Kinetics Drug Side Effects Electroretinography Emulsions Endophthalmitis Endothelial Cells Enzyme-Linked Immunosorbent Assay Exposure to Eye Family member Fluorescein Angiography Fundus photography Goals Gold Healthcare Systems Hemorrhage Histologic Histology Hydrogels Image Inflammation Injectable Injection of therapeutic agent Injections Kinetics Knowledge Lasers Macaca mulatta Measurement Measures Methods Microspheres Mitogens Modeling Monitor Morphology Needles Ophthalmic examination and evaluation Ophthalmoscopes Optical Coherence Tomography Patients Pharmaceutical Preparations Pharmacology Posterior eyeball segment structure Primates Regimen Retina Retinal Detachment Retinal Perforations Rodent Rodent Model Safety Scanning Site Sterility Techniques Technology Therapeutic Effect Time Translations VEGFA gene Vascular Endothelial Growth Factors Vascular Permeabilities angiogenesis base bevacizumab biomaterial compatibility clinical practice comparative efficacy conventional therapy drug release kinetics imaging modality in vitro Model intravitreal injection nonhuman primate ranibizumab release factor response sample collection side effect slit lamp imaging standard care

项目摘要

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.

项目总结