The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

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dc.contributor.authorYoon, Ji Youngko
dc.contributor.authorYang, Keum-Jinko
dc.contributor.authorPark, Shi-Naeko
dc.contributor.authorKim, Dong-Keeko
dc.contributor.authorKim, Jong-Dukko
dc.date.accessioned2017-01-05T07:57:39Z-
dc.date.available2017-01-05T07:57:39Z-
dc.date.created2016-12-13-
dc.date.created2016-12-13-
dc.date.issued2016-
dc.identifier.citationINTERNATIONAL JOURNAL OF NANOMEDICINE, v.11, pp.6123 - 6134-
dc.identifier.issn1178-2013-
dc.identifier.urihttp://hdl.handle.net/10203/216108-
dc.description.abstract"Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120-140 nm and a zeta potential of 20-25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine (R) reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression.-
dc.languageEnglish-
dc.publisherDOVE MEDICAL PRESS LTD-
dc.subjectDRUG-DELIVERY-
dc.subjectTARGETED DELIVERY-
dc.subjectMOUSE-
dc.subjectCELLS-
dc.subjectTRANSLOCATION-
dc.subjectPOLYMERSOMES-
dc.subjectMEMBRANE-
dc.subjectMICELLES-
dc.subjectBARRIER-
dc.subjectCARRIER-
dc.titleThe effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy-
dc.typeArticle-
dc.identifier.wosid000387820700001-
dc.identifier.scopusid2-s2.0-84996489213-
dc.type.rimsART-
dc.citation.volume11-
dc.citation.beginningpage6123-
dc.citation.endingpage6134-
dc.citation.publicationnameINTERNATIONAL JOURNAL OF NANOMEDICINE-
dc.identifier.doi10.2147/IJN.S114241-
dc.embargo.liftdate2017-04-02-
dc.embargo.terms2017-04-02-
dc.contributor.localauthorKim, Jong-Duk-
dc.contributor.nonIdAuthorYang, Keum-Jin-
dc.contributor.nonIdAuthorPark, Shi-Nae-
dc.contributor.nonIdAuthorKim, Dong-Kee-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorcell-penetrating peptide-
dc.subject.keywordAuthornanoparticle-
dc.subject.keywordAuthordexamethasone-
dc.subject.keywordAuthorgene delivery-
dc.subject.keywordAuthorbrain-derived neurotrophic factor-
dc.subject.keywordPlusDRUG-DELIVERY-
dc.subject.keywordPlusTARGETED DELIVERY-
dc.subject.keywordPlusMOUSE-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusTRANSLOCATION-
dc.subject.keywordPlusPOLYMERSOMES-
dc.subject.keywordPlusMEMBRANE-
dc.subject.keywordPlusMICELLES-
dc.subject.keywordPlusBARRIER-
dc.subject.keywordPlusCARRIER-
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