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Engineered multi-therapeutic agents delivery system towards retinal ganglion cell axon regeneration

针对视网膜神经节细胞轴突再生的工程化多治疗药物递送系统

基本信息

批准号：
10615620
负责人：
Dae Won Park
金额：
$ 38.43万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615620
关键词：
Accounting Acute Address Alkanesulfonates Artificial nanoparticles Axon Blindness Brain Cell Death Cell Survival Cell Transplantation Cell secretion Central Nervous System Charge Chelating Agents Chemicals Clinical Cytoprotection Data Development Drug Kinetics Encapsulated Engineering Environment Formulation Gel Heparin Immunohistochemistry In Vitro Inflammatory Injections Injury Ions Medical Metals Methodology Methods Modeling Motivation Nerve Crush Nerve Degeneration Nerve Regeneration Optic Nerve Optic Nerve Injuries Patients Peripheral Nerves Persons Predisposition Rattus Reaction Reporting Research Personnel Retinal Ganglion Cells Risk Side Site Solubility Survival Rate System Therapeutic Therapeutic Agents Time Transplantation Trauma Vision Visual Visualization Vitreous humor Zinc alternative treatment aqueous axon regeneration axonal degeneration chelation clinical application compliance behavior copolymer delivery vehicle experience improved in vivo intravitreal injection nanoparticle nanopolymer nerve injury neurotoxic neurotoxicity neurotrophic factor novel therapeutics optic nerve disorder pharmacologic pre-clinical preservation success therapeutic protein therapeutic target treatment strategy two photon microscopy

项目摘要

PROJECT SUMMARY In the U.S., approximately 2.2 million people suffer from optic neuropathies, accounting for 9 to 12% of all cases of blindness. Of them, 10% of patients that receive proper medical treatment continue to experience vision loss, which obviously needs an alternative treatment strategy. One of current treatments utilizes neurotrophic factors (NTFs) to increase retinal ganglion cell (RGC) survival, responsible for the visual function. While direct administration of NTFs via intravitreal injection has had some success, a susceptibility to denaturation of these NTFs limits its clinical success. Also, the delivery of NTFs alone may result in limited treatment success since optic neuropathies accompany neurodegeneration, caused by the neurotoxic cycles. To resolve these problems, we have engineered polymeric nanoparticles that mimic negatively charged sulfonate groups in natural heparin and deliver multiple therapeutic agents to continuously supply NTFs and inhibit the neurotoxicity. The advantages of our strategy include: 1) sustained delivery of NTFs at target site, mimicking continuous NTF transport, 2) prolonged bioactivity of NTFs encapsulated in the system and 3) sustained delivery of an anti-neurotoxic agent, continuously inhibiting neurodegeneration during the progression of optic neuropathies. We have constructed this application under two specific aims: (1) determine an appropriate nanoparticle formulation for the co-delivery of the multiple therapeutic agents and (2) evaluate RGC axon regeneration in rat optic nerve crush model.

项目总结