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Brain targeted nanoparticle for Alzheimer's disease therapy

用于治疗阿尔茨海默病的脑靶向纳米颗粒

基本信息

批准号：
9329544
负责人：
Peisheng Xu
金额：
$ 36.63万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9329544
关键词：
Acetylcysteine Alpha Cell Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid beta-Protein Animal Disease Models Animal Model Anti-Inflammatory Agents Anti-inflammatory Antioxidants Base of the Brain Biodistribution Biological Assay Blood - brain barrier anatomy Blood Vessels Brain C57BL/6 Mouse Cause of Death Cells Central Nervous System Diseases Characteristics Chronic Coculture Techniques Cysteine Detection Development Dose Drug Delivery Systems Drug Kinetics Drug Targeting Endothelium Environment Exhibits Fluorescent Probes Frequencies Gamma counter Glutathione Health Care Costs Human Hydrophobicity Immune response Immunotherapy In Vitro Inflammation Inflammatory Interleukin-1 beta Kinetics Learning Ligands Lipopolysaccharides Maximum Tolerated Dose Memory Microglia Mission Modeling Modification Molecular Target Multiple Sclerosis Mus NanoGel Nervous system structure Organ Oxidation-Reduction Oxidative Stress Parkinson Disease Particle Size Patients Penetration Pharmaceutical Preparations Physiological Polymers Property Reporting Research System TNF gene Testing Therapeutic Therapeutic Effect Time Tissues Toxic effect Traumatic Brain Injury United States United States National Institutes of Health base brain tissue cost crosslink cytokine density hydrophilicity hyperphosphorylated tau imaging system in vivo in vivo imaging system inhibitor/antagonist macromolecule morris water maze mouse model nanoparticle neglect public health relevance receptor reduce symptoms small molecule stimulus sensitivity success systemic toxicity targeted delivery tau Proteins therapy development

项目摘要

PROJECT SUMMARY Alzheimer’s disease (AD), which consumed ~$226 billion in health care costs in 2015, is associated with nervous system chronic inflammation. Recent research revealed that the malfunction of microglia is critical for the development of AD. Our preliminary study developed a dual targeted dual responsive nanoparticle (DTDRN) which can effectively penetrate the blood brain barrier (BBB) and release its payload in the brain. Furthermore, N-acetyl cysteine (NAC)-loaded DTDRN showed much better therapeutic effect than free NAC in a LPS-induced brain inflammatory animal model. The objective of this study is to develop a brain targeted system for AD therapy by rationally utilizing the characteristics of both BBB and the brain tissue. In Aim 1, we will develop a NAC-DTDRN and characterize its BBB penetration efficiency in vitro. Aim 2 will evaluate the anti-inflammatory and anti-oxidant effects of the NAC-DTDRN in vitro and study its pharmacokinetics in vivo. Aim 3 will test the efficiency of the NAC-DTDRN in an AD animal model and evaluate its toxicity. In summary, NAC delivery via the proposed DTDRN system which can effectively penetrate the BBB and exhibit anti- inflammatory effects has potential to benefit AD patients. Due to the versatility of DTDRN, the proposed DTDRN system can carry other therapeutic molecules (both hydrophobic and hydrophilic) to the brain and to be applied for the detection and treatment of other central nervous system diseases such as Parkinson disease, traumatic brain injury, and multiple sclerosis.

项目总结