Synthesis and Characterization of Guanidinylated Polyethylenimine-Conjugated Chitosan for Gene Delivery Systems

Kitae Ryu; Kyunghwan Kim; Tae-il Kim

Macromolecular Research, Vol.22, No.3, 264-271, March, 2014

DOI10.1007/s13233-014-2048-3 Export Citation

Synthesis and Characterization of Guanidinylated Polyethylenimine-Conjugated Chitosan for Gene Delivery Systems

Kitae Ryu¹, Kyunghwan Kim¹, and Tae-il Kim^{1, 2, †}

¹Department of Biosystems and Biomaterials Science and Engineering, College of Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea
²Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea

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In this work, guanidinylated polyethylenimine-conjugated chitosan (CS-PEI-G) was synthesized, and characterized for efficient gene delivery systems. Low molecular weight PEI (0.8 kDa) was conjugated to chitosan as a low cytotoxic template for introducing the integrated bio-functionalities and guanidine groups, which are important components of cellular penetrating peptides. Synthesized CS-PEI-G could form positively charged and nano-sized complexes with pDNA. CS-PEI-G showed enhanced transfection efficiency in comparison with unmodified CSPEI, and high transfection efficiency comparable to or higher than PEI25k, due to guanidine moieties and the serum stability of chitosan backbone. Flow cytometry results suggest that the improved transfection efficiency of CS-PEIG may be not induced by cellular uptake of polyplexes but by other factors, such as the nuclear localization ability of guanidine moieties. These results showed that the simple strategy of introducing the guanidine groups of high density to chitosan via small PEI linkers could be effective for developing efficient gene delivery carriers.

Keywords:gene delivery carriers;chitosan;low molecular weight PEI;guanidines;transfection efficiency;nuclear localization ability.

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Koping-Hogga°rd M, Tubulekas I, Guan H, Edwards K, Nilsson M, Va° rum KM, Artursson P, Gene Ther., 8, 1108 (2001)
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Jiang HL, Kim YK, Arote R, Nah JW, Cho MH, Choi YJ, Akaike T, Cho CS, J. Control. Release., 117, 273 (2007)
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Noh SM, Park MO, Shim G, Han SE, Lee HY, Huh JH, Kim MS, Choi JJ, Kim K, Kwon IC, Kim JS, Baek KH, Oh YK, J. Control. Release., 145, 159 (2010)
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Zorko M, Langel U, Adv. Drug Deliv. Rev., 57, 529 (2005)
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Tziveleka LA, Psarra AM, Tsiourvas D, Paleos CM, J.Control. Release., 117, 137 (2007)
Gao Y, Xu Z, Chen S, Gu W, Chen L, Li Y, Int. J.Pharm., 359, 241 (2008)
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Lee MJ, Cho SS, You JR, Lee Y, Kang BD, Choi JS, Park JW, Suh YL, Kim JA, Kim DK, Park JS, Gene Ther., 9, 859 (2002)
Vold IMN, Christensen BE, Carbohydr. Res., 340, 679 (2005)
Maia J, Ferreira L, Carvalho R, Ramos MA, Gil MH, Polymer, 46(23), 9604 (2005)
Rinaudo M, Polymers., 2, 505 (2010)
Huang XY, Bu HT, Jiang GB, Zeng MH, Int. J.Biol. Macromol., 49, 643 (2011)
Ahmed RA, Farghali RA, Fekry AM, Int. J. Electrochem. Sci., 7, 7270 (2012)
Mahadevan V, Lipids., 5, 563 (1970)
Zauner W, Ogris M, Wagner E, Adv. Drug Deliv. Rev., 30, 97 (1998)
Volcke C, Pirotton S, Grandfils C, Humbert C, Thiry PA, Ydens I, Dubois P, Raes M, J. Biotechnol., 125, 11 (2006)
Kim TI, Bai CZ, Nam K, Park JS, J. Control. Release., 136, 132 (2009)
Wender PA, Galliher WC, Goun EA, Jones LR, Pillow TH, Adv. Drug Deliv. Rev., 60, 452 (2008)
Jeong JH, Kim SW, Park TG, Prog. Polym. Sci., 32, 1239 (2007)

[1] Agnihotri SA, Mallikarjuna NN, Aminabhavi TM, J. Control. Release., 100, 5 (2004)

[2] Borchard G, Adv. Drug Deliv. Rev., 52, 145 (2001)

[3] Kim IY, Seo SJ, Moon HS, Yoo MK, Park IY, Kim BC, Cho CS, Biotechnol. Adv., 26, 1 (2008)

[4] Lee SJ, Park K, Oh YK, Kwon SH, Her S, Kim IS, Choi K, Lee SJ, Kim H, Lee SG, Kim K, Kwon IC, Biomaterials., 30, 2929 (2009)

[5] Koping-Hogga°rd M, Tubulekas I, Guan H, Edwards K, Nilsson M, Va° rum KM, Artursson P, Gene Ther., 8, 1108 (2001)

[6] Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS, J.Control. Release., 93, 389 (2003)

[7] Jiang HL, Kim YK, Arote R, Nah JW, Cho MH, Choi YJ, Akaike T, Cho CS, J. Control. Release., 117, 273 (2007)

[8] Jiang HL, Lim HT, Kim YK, Arote R, Shin JY, Kwon JT, Kim JE, Kim JH, Kim D, Chae C, Nah JW, Choi YJ, Cho CS, Cho MH, Eur. J. Pharm. Biopharm., 77, 36 (2011)

[9] Wong K, Sun G, Zhang X, Dai H, Liu Y, He C, Leong KW, Bioconjug. Chem., 17, 152 (2006)

[10] Noh SM, Park MO, Shim G, Han SE, Lee HY, Huh JH, Kim MS, Choi JJ, Kim K, Kwon IC, Kim JS, Baek KH, Oh YK, J. Control. Release., 145, 159 (2010)

[11] Park S, Jeong EJ, Lee J, Rhim T, Lee SK, Lee KY, Carbohydr. Polym., 92, 57 (2013)

[12] Brooks H, Lebleu B, Vives E, Adv. Drug Deliv. Rev., 57, 559 (2005)

[13] Zhao M, Weissleder R, Med. Res. Rev., 24, 1 (2004)

[14] Zorko M, Langel U, Adv. Drug Deliv. Rev., 57, 529 (2005)

[15] Funhoff AM, van Nostrum CF, Lok MC, Fretz MM, Crommelin DJA, Hennink WE, Bioconjug. Chem., 15, 1212 (2004)

[16] Kim TI, Lee M, Kim SW, Biomaterials., 31, 1798 (2010)

[17] Tziveleka LA, Psarra AM, Tsiourvas D, Paleos CM, J.Control. Release., 117, 137 (2007)

[18] Gao Y, Xu Z, Chen S, Gu W, Chen L, Li Y, Int. J.Pharm., 359, 241 (2008)

[19] Zhai XY, Sun P, Luo YF, Ma CN, Xu J, Liu WG, J. Appl. Polym. Sci., 121(6), 3569 (2011)

[20] Lee MJ, Cho SS, You JR, Lee Y, Kang BD, Choi JS, Park JW, Suh YL, Kim JA, Kim DK, Park JS, Gene Ther., 9, 859 (2002)

[21] Vold IMN, Christensen BE, Carbohydr. Res., 340, 679 (2005)

[22] Maia J, Ferreira L, Carvalho R, Ramos MA, Gil MH, Polymer, 46(23), 9604 (2005)

[23] Rinaudo M, Polymers., 2, 505 (2010)

[24] Huang XY, Bu HT, Jiang GB, Zeng MH, Int. J.Biol. Macromol., 49, 643 (2011)

[25] Ahmed RA, Farghali RA, Fekry AM, Int. J. Electrochem. Sci., 7, 7270 (2012)

[26] Mahadevan V, Lipids., 5, 563 (1970)

[27] Zauner W, Ogris M, Wagner E, Adv. Drug Deliv. Rev., 30, 97 (1998)

[28] Volcke C, Pirotton S, Grandfils C, Humbert C, Thiry PA, Ydens I, Dubois P, Raes M, J. Biotechnol., 125, 11 (2006)

[29] Kim TI, Bai CZ, Nam K, Park JS, J. Control. Release., 136, 132 (2009)

[30] Wender PA, Galliher WC, Goun EA, Jones LR, Pillow TH, Adv. Drug Deliv. Rev., 60, 452 (2008)

[31] Jeong JH, Kim SW, Park TG, Prog. Polym. Sci., 32, 1239 (2007)