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Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers

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Title: Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers
Authors: Park, Mi Ran1, Han, Ki Ok2, Han, In Kwon2, Cho, Myung Haing1,3, Nah, Jae Woon4, Choi, Yun Jaie1, Cho, Chong Su1 chocs@plaza.snu.ac.kr
Source: Journal of Controlled Release. Jul2005, Vol. 105 Issue 3, p367-380. 14p.
Subjects: Ethylene glycol, Genetic transformation, Mobile genetic elements, Cell culture
Abstract: Abstract: An ideal gene carrier requires both safety and transfection efficiency. Polyethylenimine (PEI) is a well-known cationic polymer, which has high transfection efficiency owing to its buffering capacity. But it has been reported that PEI is cytotoxic in many cell lines and non-degradable. In this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG) copolymers using Michael-type addition reactions as a new gene carrier and characterized them. These copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine particle sizes, complex formation and complex shape, respectively. Cytotoxicity and transfection efficiency of the copolymers were also checked in cultured HeLa human cervix epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human osteosarcoma cells. PEG to PEI ratio in the copolymers was near 1 and the molecular weight of the copolymer ranged from around 8000 to 12,900. These copolymers degraded rapidly at 37 °C in 0.1 M phosphate buffered saline (PBS, pH 7.4). The complete copolymer/DNA complex was formed at an N/P ratio of 12, producing a complex resistant to DNase I. Particle sizes decreased with increasing N/P ratio and PEG molecular weight, exhibiting a minimum value of 75 nm at an N/P ratio of 45 with PEI-alt-PEG (700). Cytotoxicity study showed that copolymers exhibited no cytotoxic effects on cells even at high copolymer concentration. Also, transfection efficiency was influenced by PEG molecular weight and, in case of PEI-alt-PEG (258), the transfection efficiency was higher than that for PEI 25 K in HepG2 and MG63, whereas it was lower than that for PEI 25K in HeLa cells. [Copyright &y& Elsevier]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 18131790
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers
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  Data: <searchLink fieldCode="AR" term="%22Park%2C+Mi+Ran%22">Park, Mi Ran</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Han%2C+Ki+Ok%22">Han, Ki Ok</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Han%2C+In+Kwon%22">Han, In Kwon</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Cho%2C+Myung+Haing%22">Cho, Myung Haing</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Nah%2C+Jae+Woon%22">Nah, Jae Woon</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Choi%2C+Yun+Jaie%22">Choi, Yun Jaie</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Cho%2C+Chong+Su%22">Cho, Chong Su</searchLink><relatesTo>1</relatesTo><i> chocs@plaza.snu.ac.kr</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Jul2005, Vol. 105 Issue 3, p367-380. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Ethylene+glycol%22">Ethylene glycol</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+transformation%22">Genetic transformation</searchLink><br /><searchLink fieldCode="DE" term="%22Mobile+genetic+elements%22">Mobile genetic elements</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+culture%22">Cell culture</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Abstract: An ideal gene carrier requires both safety and transfection efficiency. Polyethylenimine (PEI) is a well-known cationic polymer, which has high transfection efficiency owing to its buffering capacity. But it has been reported that PEI is cytotoxic in many cell lines and non-degradable. In this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG) copolymers using Michael-type addition reactions as a new gene carrier and characterized them. These copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine particle sizes, complex formation and complex shape, respectively. Cytotoxicity and transfection efficiency of the copolymers were also checked in cultured HeLa human cervix epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human osteosarcoma cells. PEG to PEI ratio in the copolymers was near 1 and the molecular weight of the copolymer ranged from around 8000 to 12,900. These copolymers degraded rapidly at 37 °C in 0.1 M phosphate buffered saline (PBS, pH 7.4). The complete copolymer/DNA complex was formed at an N/P ratio of 12, producing a complex resistant to DNase I. Particle sizes decreased with increasing N/P ratio and PEG molecular weight, exhibiting a minimum value of 75 nm at an N/P ratio of 45 with PEI-alt-PEG (700). Cytotoxicity study showed that copolymers exhibited no cytotoxic effects on cells even at high copolymer concentration. Also, transfection efficiency was influenced by PEG molecular weight and, in case of PEI-alt-PEG (258), the transfection efficiency was higher than that for PEI 25 K in HepG2 and MG63, whereas it was lower than that for PEI 25K in HeLa cells. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.jconrel.2005.04.008
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 14
        StartPage: 367
    Subjects:
      – SubjectFull: Ethylene glycol
        Type: general
      – SubjectFull: Genetic transformation
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      – SubjectFull: Mobile genetic elements
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      – SubjectFull: Cell culture
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    Titles:
      – TitleFull: Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers
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            NameFull: Park, Mi Ran
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            NameFull: Han, Ki Ok
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            NameFull: Han, In Kwon
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            NameFull: Cho, Myung Haing
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            NameFull: Nah, Jae Woon
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            NameFull: Choi, Yun Jaie
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              Text: Jul2005
              Type: published
              Y: 2005
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              Value: 105
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