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Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection

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dc.contributor.author Pashirova T.
dc.contributor.author Braïki A.
dc.contributor.author Zueva I.
dc.contributor.author Petrov K.
dc.contributor.author Babaev V.
dc.contributor.author Burilova E.
dc.contributor.author Samarkina D.
dc.contributor.author Rizvanov I.
dc.contributor.author Souto E.
dc.contributor.author Jean L.
dc.contributor.author Renard P.
dc.contributor.author Masson P.
dc.contributor.author Zakharova L.
dc.contributor.author Sinyashin O.
dc.date.accessioned 2019-01-22T20:35:45Z
dc.date.available 2019-01-22T20:35:45Z
dc.date.issued 2018
dc.identifier.issn 0168-3659
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/147881
dc.description.abstract © 2018 Elsevier B.V. A novel approach for brain protection against poisoning by organophosphorus agents is developed based on the combination treatment of dual delivery of two oximes. Pralidoxime chloride (2-PAM) and a novel reactivator, 6-(5-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)pentyl)-3-hydroxy picolinaldehyde oxime (3-HPA), have been loaded in solid-lipid nanoparticles (SLNs) to offer distinct release profile and systemic half-life for both oximes. To increase the therapeutic time window of both oximes, SLNs with two different compartments were designed to load each respective drug. Oxime-loaded SLNs of hydrodynamic diameter between 100 and 160 nm and negative zeta potential (−30 to −25 mV) were stable for a period of 10 months at 4 °C. SLNs displayed longer circulation time in the bloodstream compared to free 3-HPA and free 2-PAM. Oxime-loaded SLNs were suitable for intravenous (iv) administration. Paraoxon-poisoned rats (0.8 × LD50) were treated with 3-HPA-loaded SLNs and 2-PAM+3-HPA-loaded SLNs at the dose of 3-HPA and 2-PAM of 5 mg/kg. Brain AChE reactivation up to 30% was slowly achieved in 5 h after administration of 3-HPA-SLNs. For combination therapy with two oximes, a time-dependent additivity and increased reactivation up to 35% were observed.
dc.relation.ispartofseries Journal of Controlled Release
dc.subject Acetylcholinesterase
dc.subject Blood-brain barrier
dc.subject Organophosphorus agent
dc.subject Oxime
dc.subject Paraoxon
dc.subject Solid-Lipid Nanoparticles
dc.title Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection
dc.type Article
dc.relation.ispartofseries-volume 290
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 102
dc.source.id SCOPUS01683659-2018-290-SID85054708795


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  • Публикации сотрудников КФУ Scopus [22633]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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