Enhanced Gene Delivery System Using Disulfide-Linked Chitosan Immobilize with Polyamidoamine

Kihoon Nam; Ji Won Park; Heidi Bark; Jing Han; Jae-Woon Nah; Mi-Kyeong Jang; Sung Wan Kim

Macromolecular Research, Vol.22, No.4, 370-376, April, 2014

DOI10.1007/s13233-014-2052-7 Export Citation

Enhanced Gene Delivery System Using Disulfide-Linked Chitosan Immobilize with Polyamidoamine

Kihoon Nam, Ji Won Park, Heidi Bark, Jing Han, Jae-Woon Nah¹, Mi-Kyeong Jang¹, and Sung Wan Kim^†

Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112, USA
¹Department of Polymer Science and Engineering, Sunchon National University, Jeonnam, 540-742, Korea

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We developed a polyamidoamine (PAMAM) conjugated disulfide-linked chitosan (dsCS-PAM) for nonviral gene delivery. At weight ratio of 128, dsCS and dsCS-PAM showed positive zeta potential of around 9.5 mV and 14.5 mV, respectively, demonstrating their ability to form complexes with plasmid DNA (pDNA) for cell transfection. CS-PAM and dsCS-PAM formed complexes with pDNA in a reducing environment containing 5 mM DLdithiothreitol (DTT) at weight ratio 32 and 16, respectively. PAMAM conjugated chitosan derivatives, dsCS-PAM and CS-PAM, showed higher in vitro transfection efficiency than unconjugated derivatives dsCS and CS. Approximately 80% of A549 and 293 cells were viable in the presence of up to 100 μg/mL of dsCS-PAM. The results of this study demonstrate that dsCS-PAM has the potential to be a safe gene delivery carrier.

Keywords:gene delivery;chitosan;polyamidoamine;dendron.

[References]

Schmidt-Wolf GD, Schmidt-Wolf IGH, Trends Mol. Med., 9, 67 (2003)
Vijayanathan V, Thomas T, Thoma TJ, Biochemistry, 41, 14085 (2002)
Mao S, Sun W, Kisse T, Adv. Drug Deliv. Rev., 62, 12 (2010)
Kim I, Seo S, Moon H, Yoo M, Park I, Kim B, Cho C, Biotechnol. Adv., 26, 1 (2008)
Huang M, Fong C, Khor E, Lim L, J. Control. Release, 106, 391 (2005)
Choi CY, Kim DG, Jang MJ, Kim TH, Jang MK, Nah JW, J. Appl. Polym. Sci., 102(4), 3545 (2006)
Kong F, Liu G, Sun B, Zhou S, Zuo A, Zhao R, Liang D, Int. J. Pharm., 422, 445 (2012)
Rudzinski WE, Aminabha TM, Int. J. Pharm., 399, 1 (2010)
Holzerny P, Ajdini B, Heusermann W, Bruno K, Schule M, J. Control. Release., 157, 297 (2012)
Lavertu M, Methot S, Tran-Khanh N, Buschman MD, Biomaterials, 27, 4815 (2006)
Wiegand C, Winter D, Hipler UC, Skin Pharmacol. Physiol., 23, 164 (2010)
Opanasopit P, Tragulpakseerojn J, Apirakaramwong A, Ngawhirunpat T, Rojanarata T, Int. J. Pharm., 410, 161 (2006)
Ramesan RM, Sharma CP, Nanomedicine, 7, 5 (2012)
Jiang H, Kim Y, Arote R, Nah J, Cho M, Choi Y, Akaike T, Cho C, J. Control. Release, 117, 273 (2007)
Wong K, Sun G, Zhang X, Dai H, Liu Y, He C, Leong KW, Bioconjug. Chem., 17, 152 (2006)
Sarkar K, Kundu PP, Macromolecules, 51, 859 (2012)
Peng Q, Zhong Z, Zhuo R, Bioconjug. Chem., 19, 499 (2008)
Zhao QQ, Chen JL, Han M, Liang WQ, Tabata Y, Gao JQ, J. Biosci. Bioeng., 105(1), 65 (2008)

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[2] Vijayanathan V, Thomas T, Thoma TJ, Biochemistry, 41, 14085 (2002)

[3] Mao S, Sun W, Kisse T, Adv. Drug Deliv. Rev., 62, 12 (2010)

[4] Kim I, Seo S, Moon H, Yoo M, Park I, Kim B, Cho C, Biotechnol. Adv., 26, 1 (2008)

[5] Huang M, Fong C, Khor E, Lim L, J. Control. Release, 106, 391 (2005)

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[7] Kong F, Liu G, Sun B, Zhou S, Zuo A, Zhao R, Liang D, Int. J. Pharm., 422, 445 (2012)

[8] Rudzinski WE, Aminabha TM, Int. J. Pharm., 399, 1 (2010)

[9] Holzerny P, Ajdini B, Heusermann W, Bruno K, Schule M, J. Control. Release., 157, 297 (2012)

[10] Lavertu M, Methot S, Tran-Khanh N, Buschman MD, Biomaterials, 27, 4815 (2006)

[11] Wiegand C, Winter D, Hipler UC, Skin Pharmacol. Physiol., 23, 164 (2010)

[12] Opanasopit P, Tragulpakseerojn J, Apirakaramwong A, Ngawhirunpat T, Rojanarata T, Int. J. Pharm., 410, 161 (2006)

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