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dc.contributor.authorPark, Jeongmin-
dc.contributor.authorChoi, Eunshil-
dc.contributor.authorShin, Seulgi-
dc.contributor.authorLim, Sungsu-
dc.contributor.authorKim, Dohee-
dc.contributor.authorBaek, Suji-
dc.contributor.authorLee, Kang Pa-
dc.contributor.authorLee, Jae Jun-
dc.contributor.authorLee, Byeong Han-
dc.contributor.authorKim, Bokyung-
dc.contributor.authorJeong, Keunsoo-
dc.contributor.authorBaik, Ja-Hyun-
dc.contributor.authorKim, Yun Kyung-
dc.contributor.authorKim, Sehoon-
dc.date.accessioned2024-01-19T22:02:31Z-
dc.date.available2024-01-19T22:02:31Z-
dc.date.created2021-09-03-
dc.date.issued2018-08-28-
dc.identifier.issn0168-3659-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/121022-
dc.description.abstractTraumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration. MB was formulated via electrostatically/hydrophobically directed assembly with fatty acid and Pluronic surfactant (F-127 or F-68) to construct nanocomplexes of two different colloidal sizes (< 10 nm and similar to 108 nm in hydrodynamic diameter for NanoMB-127 and NanoMB-68, respectively). Compared to uncomplexed free MB, formulation into the ultrasmall nanocomplex (NanoMB-127) significantly enhanced the uptake of MB by blood-brain vascular endothelial bEnd3 cells in vitro, and indeed improved its BBB penetration upon systemic administration to normal mice in vivo. However, large-size NanoMB-68 showed negligible BBB crossing despite the efficient bEnd3 cell internalization in vitro, probably due to the unfavorable pharmacokinetic profile associated with its large particle size. By virtue of the efficient BBB penetration and cellular uptake, ultrasmall NanoMB-127 was shown to distinctively reduce the expression level of an inflammatory cytokine with no notable toxicity in vitro and also considerably prevent the neurodegeneration after TBI in mice at much lower doses than free MB. Overall, the Pluronic-supported nanocomplexation method allows efficient brain delivery of MB, offering a novel way of enhancing the efficacy of neurotherapeutics to treat brain diseases.-
dc.languageEnglish-
dc.publisherELSEVIER SCIENCE BV-
dc.subjectPLURONIC BLOCK-COPOLYMERS-
dc.subjectMETHYLENE-BLUE-
dc.subjectDRUG-
dc.subjectNANOPARTICLES-
dc.subjectDELIVERY-
dc.subjectTHERAPY-
dc.subjectCELLS-
dc.titleNootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration-
dc.typeArticle-
dc.identifier.doi10.1016/j.jconrel.2018.06.021-
dc.description.journalClass1-
dc.identifier.bibliographicCitationJOURNAL OF CONTROLLED RELEASE, v.284, pp.152 - 159-
dc.citation.titleJOURNAL OF CONTROLLED RELEASE-
dc.citation.volume284-
dc.citation.startPage152-
dc.citation.endPage159-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000441048900014-
dc.identifier.scopusid2-s2.0-85048872678-
dc.relation.journalWebOfScienceCategoryChemistry, Multidisciplinary-
dc.relation.journalWebOfScienceCategoryPharmacology & Pharmacy-
dc.relation.journalResearchAreaChemistry-
dc.relation.journalResearchAreaPharmacology & Pharmacy-
dc.type.docTypeArticle-
dc.subject.keywordPlusPLURONIC BLOCK-COPOLYMERS-
dc.subject.keywordPlusMETHYLENE-BLUE-
dc.subject.keywordPlusDRUG-
dc.subject.keywordPlusNANOPARTICLES-
dc.subject.keywordPlusDELIVERY-
dc.subject.keywordPlusTHERAPY-
dc.subject.keywordPlusCELLS-
dc.subject.keywordAuthorMethylene blue-
dc.subject.keywordAuthorPluronic block copolymer-
dc.subject.keywordAuthorBlood-brain barrier-
dc.subject.keywordAuthorNeuroprotection-
dc.subject.keywordAuthorTraumatic brain injury-
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