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Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia

Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier fo...

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Autores principales: Li, Xinxin, Li, Shuling, Ma, Chun, Li, Tieshu, Yang, Lihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045769/
https://www.ncbi.nlm.nih.gov/pubmed/35467483
http://dx.doi.org/10.1080/10717544.2022.2064564
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author Li, Xinxin
Li, Shuling
Ma, Chun
Li, Tieshu
Yang, Lihua
author_facet Li, Xinxin
Li, Shuling
Ma, Chun
Li, Tieshu
Yang, Lihua
author_sort Li, Xinxin
collection PubMed
description Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier formulation of neuroprotective agents that can be used for nose-to-brain delivery by obtaining RVG29 peptide-modified polyethylene glycol–polylactic acid-co-glycolic acid nanoparticles (PEG–PLGA RNPs) that have physicochemical properties that lead to stable and sustained drug release and thereby improve the bioavailability of neuroprotective agents. The brain-targeting ability of PEG–PLGA RNPs administered through nasal inhalation was verified in a rat model of CI. It was found that delivery to the whole brain can be achieved with little delivery to the peripheral circulation. Baicalin (BA) was selected as the neuroprotective agent for delivery. After intranasal administration of BA–PEG–PLGA RNPs, the neurological dysfunction of rats with ischemic brain injury was significantly alleviated, the cerebral infarction area was reduced, and nerve trauma and swelling were relieved. Furthermore, it was demonstrated that the neuroprotective effects of BA in a rat model of CI may be mediated by inhibition of inflammation and alleviation of oxidative stress. The immunohistochemical results obtained after treatment with nanoparticles loaded with BA showed that Nrf2/HO-1 was activated in the area in which ischemic brain damage had occurred and that its expression was significantly higher in the group treated with BA–PEG–PLGA RNPs than in the other groups. The ELISA results showed that the levels of IL-1β, IL-6, and TNF-α were abnormally increased in the serum of rats with cerebral ischemia. After treatment with BA-loaded nanoparticles, IL-1β, IL-6, and TNF-α levels decreased significantly. Oxidative stress was alleviated; the levels of glutathione and superoxide dismutase increased; and the levels of reactive oxygen species and malondialdehyde decreased, in animals to which BA–PEG–PLGA RNPs were delivered by intranasal inhalation. In conclusion, BA–PEG–PLGA RNPs can effectively deliver BA to rats and thereby exert neuroprotective effects against CI.
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spelling pubmed-90457692022-04-28 Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia Li, Xinxin Li, Shuling Ma, Chun Li, Tieshu Yang, Lihua Drug Deliv Research Article Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier formulation of neuroprotective agents that can be used for nose-to-brain delivery by obtaining RVG29 peptide-modified polyethylene glycol–polylactic acid-co-glycolic acid nanoparticles (PEG–PLGA RNPs) that have physicochemical properties that lead to stable and sustained drug release and thereby improve the bioavailability of neuroprotective agents. The brain-targeting ability of PEG–PLGA RNPs administered through nasal inhalation was verified in a rat model of CI. It was found that delivery to the whole brain can be achieved with little delivery to the peripheral circulation. Baicalin (BA) was selected as the neuroprotective agent for delivery. After intranasal administration of BA–PEG–PLGA RNPs, the neurological dysfunction of rats with ischemic brain injury was significantly alleviated, the cerebral infarction area was reduced, and nerve trauma and swelling were relieved. Furthermore, it was demonstrated that the neuroprotective effects of BA in a rat model of CI may be mediated by inhibition of inflammation and alleviation of oxidative stress. The immunohistochemical results obtained after treatment with nanoparticles loaded with BA showed that Nrf2/HO-1 was activated in the area in which ischemic brain damage had occurred and that its expression was significantly higher in the group treated with BA–PEG–PLGA RNPs than in the other groups. The ELISA results showed that the levels of IL-1β, IL-6, and TNF-α were abnormally increased in the serum of rats with cerebral ischemia. After treatment with BA-loaded nanoparticles, IL-1β, IL-6, and TNF-α levels decreased significantly. Oxidative stress was alleviated; the levels of glutathione and superoxide dismutase increased; and the levels of reactive oxygen species and malondialdehyde decreased, in animals to which BA–PEG–PLGA RNPs were delivered by intranasal inhalation. In conclusion, BA–PEG–PLGA RNPs can effectively deliver BA to rats and thereby exert neuroprotective effects against CI. Taylor & Francis 2022-04-25 /pmc/articles/PMC9045769/ /pubmed/35467483 http://dx.doi.org/10.1080/10717544.2022.2064564 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Xinxin
Li, Shuling
Ma, Chun
Li, Tieshu
Yang, Lihua
Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title_full Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title_fullStr Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title_full_unstemmed Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title_short Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
title_sort preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045769/
https://www.ncbi.nlm.nih.gov/pubmed/35467483
http://dx.doi.org/10.1080/10717544.2022.2064564
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