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      RVG29-modified microRNA-loaded nanoparticles improve ischemic brain injury by nasal delivery

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          Abstract

          Effective nose-to-brain delivery needs to be developed to treat neurodegenerative diseases. Regulating miR-124 can effectively improve the symptoms of ischemic brain injury and provide a certain protective effect from brain damage after cerebral ischemia. We used rat models of middle cerebral artery occlusion (t-MCAO) with ischemic brain injury, and we delivered RVG29-NPs-miR124 intranasally to treat neurological damage after cerebral ischemia. Rhoa and neurological scores in rats treated by intranasal administration of RVG29-PEG-PLGA/miRNA-124 were significantly lower than those in PEG-PLGA/miRNA-124 nasal administration and RVG29-PLGA/miRNA-124 nasal administration group treated rats. These results indicate that the nose-to-brain delivery of PLGA/miRNA-124 conjugated with PEG and RVG29 alleviated the symptoms of cerebral ischemia-reperfusion injury. Thus, nasal delivery of RVG29-PEG-PLGA/miRNA-124 could be a new method for treating neurodegenerative diseases.

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          Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients

          Qiuhong Ji, Yuhua Ji, Jingwen Peng … (2016)
          The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS) patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01). The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.
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            Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics

            Qingdi Zhu, Dawei Ding (2018)
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              MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia.

              Somayyeh Hamzei Taj, Widuri Kho, Adrien Riou … (2016)
              microRNA-124 (miR-124), the most abundant miRNA of the CNS, was recently shown to modulate the polarization of activated microglia and infiltrating macrophages towards the anti-inflammatory M2 phenotype and protect neurons in various ways after brain disease. In ischemic stroke, microglia and macrophages of a detrimental and persistent pro-inflammatory M1 phenotype have been shown to aggravate the secondary injury. Thus, shifting the polarization of microglia/macrophages into the beneficial, anti-inflammatory M2-like phenotype is considered neuroprotective after stroke onset. Here, we have induced 30 min transient occlusion of the right middle cerebral artery (MCAO) in 34 male, C57BL/6 mice. Lesion development was monitored with T2-weighted MRI. Liposomated miR-124 was injected in 11 animals at 48 h and in 5 animals at 10 days after MCAO. Arg-1, a marker for M2 phenotype, was co-stained with Iba-1, NeuN or GFAP. The distribution of astrocytes, neurons and microglia/macrophages and their expression of Arg-1 were quantified. Early miR-124 injection resulted in a significantly increased neuronal survival and a significantly increased number of M2-like polarized microglia/macrophages. Moreover, the lesion core, delineated by reactive astrocytes, was significantly reduced over time upon early miR-124 injection. These neuroprotective and anti-inflammatory effects of the early miR-124 treatment were pronounced during the first week with Arg-1. Number of Arg-1+ microglia/macrophages correlated with neuronal protection and with functional improvement during the first week. Thus, our present results demonstrate that miR-124 may serve as a novel therapeutic strategy for neuroprotection and functional recovery upon stroke onset.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Deliv
                Journal ID (iso-abbrev): Drug Deliv
                Journal ID (publisher-id): IDRD
                Journal ID (publisher-id): idrd20
                Title: Drug Delivery
                Publisher: Taylor & Francis
                ISSN (Print): 1071-7544
                ISSN (Electronic): 1521-0464
                Publication date Collection: 2020
                Publication date (Electronic): 13 May 2020
                Volume: 27
                Issue: 1
                Pages: 772-781
                Affiliations
                [a ]Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine , ChangChun, Jilin, China;
                [b ]School of Pharmaceutical Sciences, Jilin University , ChangChun, Jilin, China;
                [c ]Affiliated Hospital of Changchun University of Chinese medicine , ChangChun, Jilin, China
                Author notes
                CONTACT Lihua Yang ylh7239@ 123456163.com Affiliated Hospital of Changchun University of Chinese medicine , ChangChun, Jilin, China
                Article
                Publisher ID: 1760960
                DOI: 10.1080/10717544.2020.1760960
                PMC ID: 7269067
                PubMed ID: 32400219
                SO-VID: 6fc77bb8-8dea-456a-9771-efa2642c0db4
                Copyright © © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 March 2020
                Date revision received : 20 April 2020
                Date accepted : 21 April 2020
                Page count
                Figures: 5, Tables: 2, Pages: 10, Words: 6727
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: nose-to-brain,ischemic brain injury,mirna,rvg29
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: nose-to-brain, ischemic brain injury, mirna, rvg29

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