String-Like Micellar Nanoparticles Formed by Complexation of PEG- b -PPA and Plasmid DNA and Their Transfection Efficiency
Identifieur interne : 001506 ( Main/Exploration ); précédent : 001505; suivant : 001507String-Like Micellar Nanoparticles Formed by Complexation of PEG- b -PPA and Plasmid DNA and Their Transfection Efficiency
Auteurs : Xuan Jiang [États-Unis] ; Derek Leong [États-Unis] ; Yong Ren [États-Unis] ; Zhiping Li [États-Unis] ; Michael S. Torbenson [États-Unis] ; Hai-Quan Mao [États-Unis]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2011-06-01.
English descriptors
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Abstract
ABSTRACT: Purpose: To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion. Methods: PEG-b-PPA/DNA micellar nanoparticles were prepared in aqueous solution through spontaneous self-assembly between plasmid DNA and PEG10K-b-PPA4K or PEG10K-b-PP13K polymer. The stability of these micellar nanoparticles in different physiological media was evaluated by monitoring the particle size change of micellar nanoparticles with dynamic light scattering (DLS). The transfection efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver was examined and compared with that of PPA/DNA nanoparticles after intravenous and intrabiliary infusion. Results: These PEG-b-PPA/DNA micellar nanoparticles exhibited unique string-like morphology under TEM. The stability of these string-like nanoparticles in salt-, serum- or bile- containing media was significantly improved compared with PPA/DNA nanoparticles. More importantly, these PEG-b-PPA/DNA nanoparticles mediated 10-fold higher transfection efficiency than PPA/DNA nanoparticles in rat liver when delivered via intrabiliary infusion. In addition, histopathological data revealed that the PEG-b-PPA/DNA nanoparticles induced minimal level of liver toxicity or damage. Conclusions: These string-like PEG-b-PPA/DNA micelles can mediate efficient transgene expression in the liver after bile duct infusion, and they have great potential to be used as effective gene carriers for liver-targeted gene delivery.
Url:
DOI: 10.1007/s11095-011-0436-3
Affiliations:
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Torbenson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, 21231, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mao, Hai Quan" sort="Mao, Hai Quan" uniqKey="Mao H" first="Hai-Quan" last="Mao">Hai-Quan Mao</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><publisher>Springer US; http://www.springer-ny.com</publisher><pubPlace>Boston</pubPlace><date type="published" when="2011-06-01">2011-06-01</date><biblScope unit="volume">28</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1317">1317</biblScope><biblScope unit="page" to="1327">1327</biblScope></imprint><idno type="ISSN">0724-8741</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0724-8741</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DNA micellar nanoparticles</term><term>block copolymer</term><term>liver-targeted gene delivery</term><term>morphology</term><term>string-like</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">ABSTRACT: Purpose: To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion. Methods: PEG-b-PPA/DNA micellar nanoparticles were prepared in aqueous solution through spontaneous self-assembly between plasmid DNA and PEG10K-b-PPA4K or PEG10K-b-PP13K polymer. The stability of these micellar nanoparticles in different physiological media was evaluated by monitoring the particle size change of micellar nanoparticles with dynamic light scattering (DLS). The transfection efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver was examined and compared with that of PPA/DNA nanoparticles after intravenous and intrabiliary infusion. Results: These PEG-b-PPA/DNA micellar nanoparticles exhibited unique string-like morphology under TEM. The stability of these string-like nanoparticles in salt-, serum- or bile- containing media was significantly improved compared with PPA/DNA nanoparticles. More importantly, these PEG-b-PPA/DNA nanoparticles mediated 10-fold higher transfection efficiency than PPA/DNA nanoparticles in rat liver when delivered via intrabiliary infusion. In addition, histopathological data revealed that the PEG-b-PPA/DNA nanoparticles induced minimal level of liver toxicity or damage. Conclusions: These string-like PEG-b-PPA/DNA micelles can mediate efficient transgene expression in the liver after bile duct infusion, and they have great potential to be used as effective gene carriers for liver-targeted gene delivery.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Jiang, Xuan" sort="Jiang, Xuan" uniqKey="Jiang X" first="Xuan" last="Jiang">Xuan Jiang</name></region><name sortKey="Leong, Derek" sort="Leong, Derek" uniqKey="Leong D" first="Derek" last="Leong">Derek Leong</name><name sortKey="Li, Zhiping" sort="Li, Zhiping" uniqKey="Li Z" first="Zhiping" last="Li">Zhiping Li</name><name sortKey="Mao, Hai Quan" sort="Mao, Hai Quan" uniqKey="Mao H" first="Hai-Quan" last="Mao">Hai-Quan Mao</name><name sortKey="Mao, Hai Quan" sort="Mao, Hai Quan" uniqKey="Mao H" first="Hai-Quan" last="Mao">Hai-Quan Mao</name><name sortKey="Ren, Yong" sort="Ren, Yong" uniqKey="Ren Y" first="Yong" last="Ren">Yong Ren</name><name sortKey="Torbenson, Michael S" sort="Torbenson, Michael S" uniqKey="Torbenson M" first="Michael S." last="Torbenson">Michael S. Torbenson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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