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:
- 金额:$ 36.63万
- 依托单位:
- 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:
- 关键词:AcetylcysteineAlpha CellAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmyloid beta-ProteinAnimal Disease ModelsAnimal ModelAnti-Inflammatory AgentsAnti-inflammatoryAntioxidantsBase of the BrainBiodistributionBiological AssayBlood - brain barrier anatomyBlood VesselsBrainC57BL/6 MouseCause of DeathCellsCentral Nervous System DiseasesCharacteristicsChronicCoculture TechniquesCysteineDetectionDevelopmentDoseDrug Delivery SystemsDrug KineticsDrug TargetingEndotheliumEnvironmentExhibitsFluorescent ProbesFrequenciesGamma counterGlutathioneHealth Care CostsHumanHydrophobicityImmune responseImmunotherapyIn VitroInflammationInflammatoryInterleukin-1 betaKineticsLearningLigandsLipopolysaccharidesMaximum Tolerated DoseMemoryMicrogliaMissionModelingModificationMolecular TargetMultiple SclerosisMusNanoGelNervous system structureOrganOxidation-ReductionOxidative StressParkinson DiseaseParticle SizePatientsPenetrationPharmaceutical PreparationsPhysiologicalPolymersPropertyReportingResearchSystemTNF geneTestingTherapeuticTherapeutic EffectTimeTissuesToxic effectTraumatic Brain InjuryUnited StatesUnited States National Institutes of Healthbasebrain tissuecostcrosslinkcytokinedensityhydrophilicityhyperphosphorylated tauimaging systemin vivoin vivo imaging systeminhibitor/antagonistmacromoleculemorris water mazemouse modelnanoparticleneglectpublic health relevancereceptorreduce symptomssmall moleculestimulus sensitivitysuccesssystemic toxicitytargeted deliverytau Proteinstherapy 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.
项目摘要
阿尔茨海默病(AD)在2015年消耗了约2260亿美元的医疗保健费用,
神经系统慢性炎症。最近的研究表明,小胶质细胞的功能障碍是关键,
AD的发展。我们的初步研究开发了一种双靶向双响应纳米颗粒,
(DTDRN),其可以有效地穿透血脑屏障(BBB)并在脑中释放其有效载荷。
此外,N-乙酰半胱氨酸(NAC)负载的DTDRN显示出比游离NAC更好的治疗效果。
LPS诱导的脑炎症动物模型。这项研究的目的是开发一种针对
合理利用血脑屏障和脑组织的特点,建立AD治疗系统。目标1:
将开发NAC-DTDRN并在体外表征其BBB穿透效率。目标2将评估
体外抗炎和抗氧化作用,并研究其体内药代动力学。
目的3:在AD动物模型中检测NAC-DTDRN的有效性并评价其毒性。总的来说,
通过所提出的DTDRN系统递送NAC,该系统可以有效地穿透BBB并表现出抗-
炎症作用有可能使AD患者受益。由于DTDRN的多功能性,建议
DTDRN系统可以将其他治疗分子(疏水性和亲水性)携带到大脑,
可用于检测和治疗其他中枢神经系统疾病,如帕金森病
疾病、创伤性脑损伤和多发性硬化症。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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Peisheng Xu其他文献
Peisheng Xu的其他文献
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{{ truncateString('Peisheng Xu', 18)}}的其他基金
Cancer cell selective killing nanoparticle for advanced ovarian cancer treatment
癌细胞选择性杀伤纳米颗粒用于晚期卵巢癌治疗
- 批准号:
10680585 - 财政年份:2022
- 资助金额:
$ 36.63万 - 项目类别:
Cancer cell selective killing nanoparticle for advanced ovarian cancer treatment
癌细胞选择性杀伤纳米颗粒用于晚期卵巢癌治疗
- 批准号:
10453919 - 财政年份:2022
- 资助金额:
$ 36.63万 - 项目类别:
The development of a multifunctional nanoenzyme for AD treatment
用于AD治疗的多功能纳米酶的开发
- 批准号:
10611675 - 财政年份:2022
- 资助金额:
$ 36.63万 - 项目类别:
Nano-cocktail overcomes multidrug-resistance for ovarian cancer therapy
纳米鸡尾酒克服了卵巢癌治疗的多重耐药性
- 批准号:
8958102 - 财政年份:2015
- 资助金额:
$ 36.63万 - 项目类别:
Dual responsive nanoparticle for brain targeted drug delivery
用于大脑靶向药物输送的双响应纳米颗粒
- 批准号:
8653312 - 财政年份:
- 资助金额:
$ 36.63万 - 项目类别:
Dual responsive nanoparticle for brain targeted drug delivery
用于大脑靶向药物输送的双响应纳米颗粒
- 批准号:
8885856 - 财政年份:
- 资助金额:
$ 36.63万 - 项目类别:
Dual responsive nanoparticle for brain targeted drug delivery
用于大脑靶向药物输送的双响应纳米颗粒
- 批准号:
9061734 - 财政年份:
- 资助金额:
$ 36.63万 - 项目类别:
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