Dataset Information

Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases.

ABSTRACT: Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer's disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potential in the treatment of cerebral ischemia and Alzheimer's disease. To prevent the decline of miR132 of miR132 levels in the blood, we used mouse and rat models of Alzheimer's disease with ischemic brain injury, and then delivered Wheat germ agglutinin (WGA)-NPs-miR132 intranasally to treat neurological damage after cerebral ischemia. Synaptic protein expression levels in Alzheimer's mouse models increased significantly after administration. We propose that, nasal delivery of WGA-NPs-miR132 is an interesting novel therapeutic approach for the treatment of neurodegenerative diseases.

SUBMITTER: Su Y

PROVIDER: S-EPMC7424054 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases.

Su Yu Y Sun Bixi B Gao Xiaoshu X Dong Xinyue X Fu Lanbo L Zhang Yingxin Y Li Zhulin Z Wang Yue Y Jiang Hongyu H Han Bing B

Frontiers in pharmacology 20200806

Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer's disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potentia ...[more]

PMID: 32848773

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Project description:BackgroundCancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin.Methodology/principal findingsApotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano), and showed further increase in dimension (75-95 etam) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver.ConclusionsThe present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney.

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Dataset Information

Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases.

Publications

Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases.

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