Low Molecular Weight PEI Conjugated Pluronic Copolymer: Useful Additive for Enhancing Gene Transfection Efficiency

Kyung Chul Cho; Seung Ho Choi; Tae Gwan Park

Macromolecular Research, Vol.14, No.3, 348-353, June, 2006

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Low Molecular Weight PEI Conjugated Pluronic Copolymer: Useful Additive for Enhancing Gene Transfection Efficiency

Kyung Chul Cho, Seung Ho Choi, and Tae Gwan Park^†

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea

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For enhancing the gene delivery efficiency of polyplexes, a new formulation was developed using PEI conjugated Pluronic F127 copolymer as an effective additive. Low molecular weight, branched polyethylenimine Mw 600 (LMW BPEI 600) was conjugated to the terminal end of Pluronic F127. The PEI-modified Pluronic copolymers formed a micellar structure in aqueous solution, similar to that of unmodified Pluronic copolymer. PEI modification of Pluronic copolymer increased the size of micelles while concomitantly raising the critical micelle concentration (CMC). The PEI-modified Pluronic copolymer was used as a micellar additive to enhance the gene transfection efficiency of pre-formulated polyelectrolyte complex nanoparticles composed of luciferase plasmid DNA and branched PEI Mw 25k (BPEI 25k) or polylysine Mw 39k (PLL 39k). The luciferase gene expression levels were significantly enhanced by the addition of the BPEI-modified Pluronic copolymer for the two formulations of BPEI and PLL polyplexes. The results indicated that the BPEI-modified Pluronic copolymer micelles ionically interacted on the surface of DNA/ BPEI (PLL) polyplexes which might facilitate cellular uptake process.

Keywords:gene delivery;Pluronic;polyethylenimine;polyplexes;transfection

[References]

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Smedt SC, Demeester J, Hennink WE, Pharm. Res., 17, 113 (2002)
Ledley FD, Hum. Gene Ther., 6, 1129 (1996)
Boussif O, Lezoualch F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci. USA, 92, 7297 (1995)
Zanta MA, Boussif O, Adib A, Behr JP, Bioconjugate Chem., 8, 839 (1997)
Godbey WT, Wu KK, Mikos AG, J. Control. Release, 60, 149 (1999)
Kircheis R, Kichler A, Wallner G, Kursa M, Ogris M, Felzmann T, Buchberger M, Wagner E, Gene Ther., 4, 409 (1997)
Ferrari S, Moro E, Pettenazzo A, Behr JP, Zacchello F, Scarpa M, Gene Ther., 4, 1100 (1997)
Boletta A, Benigni A, Lutz J, Remuzzi G, Soria MR, Monaco L, Hum. Gene Ther., 8, 1243 (1997)
Tang MX, Szoka FC, Gene Ther., 4, 823 (1997)
Cho KC, Kim SH, Jeong JH, Park TG, Macromol. Biosci., 5, 512 (2005)
Lee H, Jeong JH, Park TG, J. Control. Release, 76, 183 (2001)
Tang GP, Zeng JM, Gao SJ, Ma YX, Shi L, Li Y, Too HP, Wang S, Biomaterials, 24, 2351 (2003)
Kim EM, Jeong HJ, Park IK, Cho CS, Bom HS, Kim CG, Nucl. Med. Biol., 31, 781 (2004)
Li J, Carlsson J, Lin J, Caldwell KD, Bioconjugate Chem., 7, 592 (1996)
Kataoka K, Togawa H, Harada A, Yasugi K, Matsumoto T, Katayose S, Macromolecules, 29(26), 8556 (1996)
Kabanov AV, Sriadibhatla S, Gebhart CL, Yang Z, Alakhov VY, Polymer Reprints, 45, 392 (2004)
Belenkov AI, Alakhov VY, Vinogradov SV, panasci LC, Monia BP, Chow TYK, Gene Ther., 11, 1665 (2004)
Astafieva I, Maksimova I, Lukanidin E, Alakhov V, Kabanov A, Febs Lett., 389, 278 (1996)
Gebhart CL, Sriadibhatla S, Vinogradov S, Lemieux P, Alakhov V, Kabanov AV, Bioconjugate Chem., 7, 592 (1996)
Kabanov AV, Lemieux P, Vinogradov S, Alakhov V, Adv. Drug Deliv. Rev., 54, 223 (2002)
Ochietti B, Guerin N, Vinogradov SV, St-Pierre Y, Lemieux P, Kabanov AV, Alakhov VY, J. Drug Target., 10, 113 (2002)
Jeong JH, Kim SW, Park TG, Pharm. Res., 21, 50 (2004)
Sambrook J, Fritsch EF, Maniatis T, Molecular Cloning,Cold Spring Harbor Laboratory Press, Plainview, NY. J. Vol. 1, pp1.33-1.52 (1989)
Li J, Carlsson J, Lin J, Caldwell KD, Bioconjugate Chem., 7, 592 (1996)
Mikulec LJ, Puleo DA, J. Biomed. Mater. Res., 32, 203 (2004)
Jeong JH, Byun YR, Park TG, J. Biomater. Sci.-Polym. Ed., 14, 1 (2003)
Kim HK, Park TG, Macromol. Rapid Commun., 23, 26 (2002)
Kim SH, Jeong JH, Cho KC, Kim SW, Park TG, J. Control. Release, 104, 223 (2005)

[Referenced By]

[1] Merdan T, Kopecek J, Kissel T, Adv. Drug Deliv. Rev., 54, 715 (2002)

[2] Smedt SC, Demeester J, Hennink WE, Pharm. Res., 17, 113 (2002)

[3] Ledley FD, Hum. Gene Ther., 6, 1129 (1996)

[4] Boussif O, Lezoualch F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci. USA, 92, 7297 (1995)

[5] Zanta MA, Boussif O, Adib A, Behr JP, Bioconjugate Chem., 8, 839 (1997)

[6] Godbey WT, Wu KK, Mikos AG, J. Control. Release, 60, 149 (1999)

[7] Kircheis R, Kichler A, Wallner G, Kursa M, Ogris M, Felzmann T, Buchberger M, Wagner E, Gene Ther., 4, 409 (1997)

[8] Ferrari S, Moro E, Pettenazzo A, Behr JP, Zacchello F, Scarpa M, Gene Ther., 4, 1100 (1997)

[9] Boletta A, Benigni A, Lutz J, Remuzzi G, Soria MR, Monaco L, Hum. Gene Ther., 8, 1243 (1997)

[10] Tang MX, Szoka FC, Gene Ther., 4, 823 (1997)

[11] Cho KC, Kim SH, Jeong JH, Park TG, Macromol. Biosci., 5, 512 (2005)

[12] Lee H, Jeong JH, Park TG, J. Control. Release, 76, 183 (2001)

[13] Tang GP, Zeng JM, Gao SJ, Ma YX, Shi L, Li Y, Too HP, Wang S, Biomaterials, 24, 2351 (2003)

[14] Kim EM, Jeong HJ, Park IK, Cho CS, Bom HS, Kim CG, Nucl. Med. Biol., 31, 781 (2004)

[15] Li J, Carlsson J, Lin J, Caldwell KD, Bioconjugate Chem., 7, 592 (1996)

[16] Kataoka K, Togawa H, Harada A, Yasugi K, Matsumoto T, Katayose S, Macromolecules, 29(26), 8556 (1996)

[17] Kabanov AV, Sriadibhatla S, Gebhart CL, Yang Z, Alakhov VY, Polymer Reprints, 45, 392 (2004)

[18] Belenkov AI, Alakhov VY, Vinogradov SV, panasci LC, Monia BP, Chow TYK, Gene Ther., 11, 1665 (2004)

[19] Astafieva I, Maksimova I, Lukanidin E, Alakhov V, Kabanov A, Febs Lett., 389, 278 (1996)

[20] Gebhart CL, Sriadibhatla S, Vinogradov S, Lemieux P, Alakhov V, Kabanov AV, Bioconjugate Chem., 7, 592 (1996)

[21] Kabanov AV, Lemieux P, Vinogradov S, Alakhov V, Adv. Drug Deliv. Rev., 54, 223 (2002)

[22] Ochietti B, Guerin N, Vinogradov SV, St-Pierre Y, Lemieux P, Kabanov AV, Alakhov VY, J. Drug Target., 10, 113 (2002)

[23] Jeong JH, Kim SW, Park TG, Pharm. Res., 21, 50 (2004)

[24] Sambrook J, Fritsch EF, Maniatis T, Molecular Cloning,Cold Spring Harbor Laboratory Press, Plainview, NY. J. Vol. 1, pp1.33-1.52 (1989)

[25] Li J, Carlsson J, Lin J, Caldwell KD, Bioconjugate Chem., 7, 592 (1996)

[26] Mikulec LJ, Puleo DA, J. Biomed. Mater. Res., 32, 203 (2004)

[27] Jeong JH, Byun YR, Park TG, J. Biomater. Sci.-Polym. Ed., 14, 1 (2003)

[28] Kim HK, Park TG, Macromol. Rapid Commun., 23, 26 (2002)

[29] Kim SH, Jeong JH, Cho KC, Kim SW, Park TG, J. Control. Release, 104, 223 (2005)