Water-Soluble Lipopolymer for Gene Delivery
Identifieur interne : 002256 ( Main/Exploration ); précédent : 002255; suivant : 002257Water-Soluble Lipopolymer for Gene Delivery
Auteurs : Sang-Oh Han [États-Unis] ; Ram I. Mahato [États-Unis] ; Sung Wan Kim [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 2001.
Abstract
The use of biocompatible polymeric gene carriers may overcome the current problems associated with viral vectors in safety, immunogenicity, and mutagenesis. Nontoxic water-soluble lipopolymer (WSLP), poly{(ethylenimine)-co-[N-(2-aminoethyl) ethyleneimin]-co-N-(N-cholesteryloxycarbonyl-(2-aminoethyl)ethylenimine)} was synthesized using branched poly(ethylenimine) (PEI, mw 1800) and cholesteryl chloroformate. Following synthesis and purification, the structure and molecular weight of WSLP were confirmed by 1H NMR and MADI-TOF mass spectrometry, respectively. The percentage of cholesterol conjugated to PEI was about 47%, and the average molecular weight of WSLP was approximately 2000 Da. WSLP/pDNA complexes were prepared at different N/P (nitrogen atoms of WSLP/phosphate of plasmid DNA) ratios and characterized in terms of particle size, ζ potential, osmolarity, surface morphology, and cytotoxicity. WSLP condensed plasmid DNA when N/P ratio reached 2.5/1 and no free DNA was detected at N/P ratio of 5/1 and above, as determined by agarose gel electrophoresis. The mean particle size was in the range of 25.9 to 148.5 nm and was dependent on N/P ratios. Atomic force microscopy (AFM) showed complete condensation of plasmid DNA with spherical particles of ∼50 nm in diameter. WSLP/pDNA complexes or WSLP itself were nontoxic to CT-26 colon adenocarcinoma and 293 T human embryonic kidney transformed cells when formulated at the N/P ratio of 10/1 and below as determined by MTT assay. In contrast, PEI25000/pDNA complexes were toxic to these cells. Erythrocytes aggregated when incubated with PEI25000/pCMV−Luc complexes at high DNA concentrations, but there was little aggregation with WSLP/pCMV−Luc complexes. WSLP/pCMV−Luc complexes demonstrated higher transfection efficiency in both CT-26 and 293 T cells compared to PEI25000- or PEI1800-based formulations. WSLP/pCMV−Luc complexes are nontoxic and showed enhanced in vitro transfection. Thus, WSLP will be a suitable carrier for in vivo gene delivery.
Url:
DOI: 10.1021/bc000120w
Affiliations:
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Mahato</name></author><author><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6A5C65CBFC2E0F67FB5925B63FC96F31CADCD295</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1021/bc000120w</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-V781JTWS-D/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">002B75</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002B75</idno><idno type="wicri:Area/Istex/Curation">002B75</idno><idno type="wicri:Area/Istex/Checkpoint">001079</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001079</idno><idno type="wicri:doubleKey">1043-1802:2001:Han S:water:soluble:lipopolymer</idno><idno type="wicri:Area/Main/Merge">002280</idno><idno type="wicri:Area/Main/Curation">002256</idno><idno type="wicri:Area/Main/Exploration">002256</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Water-Soluble Lipopolymer for Gene Delivery</title><author><name sortKey="Han, Sang Oh" sort="Han, Sang Oh" uniqKey="Han S" first="Sang-Oh" last="Han">Sang-Oh Han</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry,University of Utah, Salt Lake City</wicri:cityArea></affiliation></author><author><name sortKey="Mahato, Ram I" sort="Mahato, Ram I" uniqKey="Mahato R" first="Ram I." last="Mahato">Ram I. Mahato</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry,University of Utah, Salt Lake City</wicri:cityArea></affiliation></author><author><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry,University of Utah, Salt Lake City</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country><wicri:regionArea> To whom all correspondence should be addressed: SungWan Kim, Center for Controlled Chemical Delivery (CCCD),Department of Pharmaceutics and Pharmaceutical Chemistry,University of Utah, BPRB, Room 205, Salt Lake City, UT 84112.Phone: 801-581-6801, Fax: 801-581-7848</wicri:regionArea><wicri:noRegion>Fax: 801-581-7848</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Bioconjugate Chemistry</title><title level="j" type="abbrev">Bioconjugate Chem.</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2001-04-21">2001</date><date when="2001-05-16">2001</date><biblScope unit="vol">12</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="337">337</biblScope><biblScope unit="page" to="345">345</biblScope></imprint><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1043-1802</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The use of biocompatible polymeric gene carriers may overcome the current problems associated with viral vectors in safety, immunogenicity, and mutagenesis. Nontoxic water-soluble lipopolymer (WSLP), poly{(ethylenimine)-co-[N-(2-aminoethyl) ethyleneimin]-co-N-(N-cholesteryloxycarbonyl-(2-aminoethyl)ethylenimine)} was synthesized using branched poly(ethylenimine) (PEI, mw 1800) and cholesteryl chloroformate. Following synthesis and purification, the structure and molecular weight of WSLP were confirmed by 1H NMR and MADI-TOF mass spectrometry, respectively. The percentage of cholesterol conjugated to PEI was about 47%, and the average molecular weight of WSLP was approximately 2000 Da. WSLP/pDNA complexes were prepared at different N/P (nitrogen atoms of WSLP/phosphate of plasmid DNA) ratios and characterized in terms of particle size, ζ potential, osmolarity, surface morphology, and cytotoxicity. WSLP condensed plasmid DNA when N/P ratio reached 2.5/1 and no free DNA was detected at N/P ratio of 5/1 and above, as determined by agarose gel electrophoresis. The mean particle size was in the range of 25.9 to 148.5 nm and was dependent on N/P ratios. Atomic force microscopy (AFM) showed complete condensation of plasmid DNA with spherical particles of ∼50 nm in diameter. WSLP/pDNA complexes or WSLP itself were nontoxic to CT-26 colon adenocarcinoma and 293 T human embryonic kidney transformed cells when formulated at the N/P ratio of 10/1 and below as determined by MTT assay. In contrast, PEI25000/pDNA complexes were toxic to these cells. Erythrocytes aggregated when incubated with PEI25000/pCMV−Luc complexes at high DNA concentrations, but there was little aggregation with WSLP/pCMV−Luc complexes. WSLP/pCMV−Luc complexes demonstrated higher transfection efficiency in both CT-26 and 293 T cells compared to PEI25000- or PEI1800-based formulations. WSLP/pCMV−Luc complexes are nontoxic and showed enhanced in vitro transfection. Thus, WSLP will be a suitable carrier for in vivo gene delivery.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Utah</li></region></list><tree><country name="États-Unis"><region name="Utah"><name sortKey="Han, Sang Oh" sort="Han, Sang Oh" uniqKey="Han S" first="Sang-Oh" last="Han">Sang-Oh Han</name></region><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name><name sortKey="Mahato, Ram I" sort="Mahato, Ram I" uniqKey="Mahato R" first="Ram I." last="Mahato">Ram I. Mahato</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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