Research progress of chitosan derivatives as gene delivery vector

LI Yan

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Volume 29 Issue 1

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2011 > 29(1): 8-10,61

LI Yan. Research progress of chitosan derivatives as gene delivery vector[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 8-10,61.

Citation:

LI Yan. Research progress of chitosan derivatives as gene delivery vector[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 8-10,61.

Research progress of chitosan derivatives as gene delivery vector

LI Yan

Department of Pharmacy, 411th Hospital of PLA, Shanghai 200081,China

Received Date: 2010-09-20
Rev Recd Date: 2010-10-21

Abstract

Despite the advantages of chitosan as a non-viral gene delivery vector, the application of this system is significantly limited by its poor solubility (the amino groups on chitosan are only partially protonated at physiological pH 7.4), poor stability of the polyplex at physiological pH, low cell specificity and therefore low transfection efficiency. Chitosan structure modification or additive incorporation is an effective way to improve the stability of the polyplex in biological fluids, enhance targeted cell delivery and facilitate endo-lysosomal release of the complex. In this paper, chitosan derivatives as gene delivery vector were reviewed to facilitate the process of chitosan vector development for clinical application.
- gene delivery vector,
- chitosan,
- derivative

References

[1]	Brus C, Petersen H, Aigner A, et al. Efficiency of polyethylenimines and polyethyleniminegraft-poly (ethylene glycol) block copolymers to protect oligonucleotides against enzymatic degradation[J]. Eur.J Pharm Biopharm, 2004, (57): 427.
[2]	Fischer D, Osburg B, Petersen H, et al. Effect of poly(ethyleneimine) molecular weight and pegylation on organ distribution and pharmacokinetics of polyplexes with oligodeoxynucleotides in mice[J]. Drug Metab Dispos,2004, (32): 983.
[3]	Mao S, Neu M, Germershaus O, et al. Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes[J]. Bioconjug Chem, 2006 ,(17) : 1209.
[4]	Kunath K, von Harpe A, Petersen H, et al. The structure of PEG-modified poly(ethylene imines) influences biodistribution and pharmacokinetics of their complexes with NF-kappaB decoy in mice[J].Pharm Res,2002, (19) : 810.
[5]	Zhang Y, Chen J, Zhang Y, et al. A novel PEGylation of chitosan nanoparticles for gene delivery[J].Biotechnol Appl Biochem, 2007 ,(46) :197.
[6]	Zhang H, Mardyani S, Chan WC, et al.Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics[J]. Biomacromolecules,2006, (7) :1568.
[7]	Kim TH, Nah JW, Cho MH, et al. Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles[J]. J Nanosci Nanotechnol,2006, (6) :2796.
[8]	Park IK, Kim TH, Park YH, et al. Galactosylated chitosan-graft-poly(ethylene glycol) as hepatocyte-targeting DNA carrier[J]. J Control Release,2001,(76): 349.
[9]	Mansouri S, Cuie Y, Winnik , et al. Characterization of folate-chitosan-DNA nanoparticles for gene therapy[J].Biomaterials,2006, (27) :2060..
[10]	Jiang H, Kwon J, Kim E, et al. Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting[J]. J Control Release, 2008, (131) :150.
[11]	Schaffer DV, Lauffenburger DA, Optimization of cell surface binding enhances efficiency and specificity of molecular conjugate gene delivery[J]. J Biol Chem,1998, (273) :28004.
[12]	Benns JM, Choi JS, Mahato RI, et al. pH sensitive cationic polymer gene delivery vehicle: N-Acpoly( L-histidine)-graft-poly(L-lysine) comb shaped polymer[J]. Bioconjug Chem,2000, (11): 637.
[13]	Li W, Nicol F, Szoka Jr FC, GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery[J]. Adv Drug Deliv Rev, 2004, (56) :967.
[14]	Wagner E, Effects of membrane-active agents in gene delivery[J].J Control Release, 1998, (53) :155.
[15]	Jones RA, Cheung CY, Black FE, et al. Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pHsensitive disruption of endosomal vesicles[J]. Biochem J, 2003, (372) :65.
[16]	Kim TH, Kim SI, Akaike T, et al. Synergistic effect of poly(ethylenimine) on the transfection efficiency of galactosylated chitosan/DNA complexes[J].J Control Release, 2005, (105) :354.
[17]	Thanou M, Florea BI, Geldof M, et al. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines[J]. Biomaterials, 2002, (23): 153.
[18]	Mao S, Shuai X, Unger F, et al. Synthesis, characterization and cytotoxicity of poly (ethylene glycol)-graft-trimethyl chitosan block copolymers[J]. Biomaterials, 2005,(26) : 6343.
[19]	Satoh T, Kano H, Nakatani M, et al. 6-Amino-6-deoxy chitosan. Sequential chemical modifications at the C-6 positions of N-phthaloylchitosan and evaluation as a gene carrier[J].Carbohydr Res,. 2006, (341) : 2406.
[20]	Park IK, Ihm JE, Park YH, et al. Galactosylated chitosan(GC)-graftpoly(vinyl pyrrolidone) (PVP) as hepatocytetargeting DNA carrier: preparation and physicochemical characterization of GCgraft-PVP/DNA complex (1) [J]. J Control Release,2003, (86) : 349.
[21]	Wong K, Sun G, Zhang X, et al. PEI-g-chitosan, a novel gene delivery system with transfection efficiency comparable to polyethylenimine in vitro and after liver administration in vivo[J].Bioconjug Chem,2006, (17) : 152.
[22]	Kurisawa M, Yokoyama M, Okano T, Transfection efficiency increases by incorporating hydrophobicmonomer units into polymeric gene carriers[J].J Control Release,2000, (68) : 1.
[23]	Kim YH, Gihm SH, Park CR, et al. Structural characteristics of size-controlled self aggregates of deoxycholic acidmodified chitosan and their application as a DNA delivery carrier[J].Bioconjugate Chem,2001 ,(12) : 932.
[24]	Liu WG, Zhang X, Sun SJ, et al. N-alkylated chitosan as a potential nonviral vector for gene transfection[J]. Bioconjugate Chem,2003, (14) : 782.
[25]	Hu F, Zhao M, Yuan H, et al. A novel chitosan oligosaccharidestearic acid micelles for gene delivery: properties and in vitro transfection studies[J]. Int J Pharm,2006,(315) : 158.
[26]	Mao Z, Ma L, Yan J, et al. The gene transfection efficiency of thermoresponsive N, N, N-trimethyl chitosan chloride-g-poly(N-isopropylacrylamide) copolymer[J]. Biomaterials,2007, (28) : 4488.

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Research progress of chitosan derivatives as gene delivery vector

Department of Pharmacy, 411th Hospital of PLA, Shanghai 200081,China

Received Date: 2010-09-20

Rev Recd Date: 2010-10-21

Key words:

Abstract: Despite the advantages of chitosan as a non-viral gene delivery vector, the application of this system is significantly limited by its poor solubility (the amino groups on chitosan are only partially protonated at physiological pH 7.4), poor stability of the polyplex at physiological pH, low cell specificity and therefore low transfection efficiency. Chitosan structure modification or additive incorporation is an effective way to improve the stability of the polyplex in biological fluids, enhance targeted cell delivery and facilitate endo-lysosomal release of the complex. In this paper, chitosan derivatives as gene delivery vector were reviewed to facilitate the process of chitosan vector development for clinical application.

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Reference (26)

[1]	Brus C, Petersen H, Aigner A, et al. Efficiency of polyethylenimines and polyethyleniminegraft-poly (ethylene glycol) block copolymers to protect oligonucleotides against enzymatic degradation[J]. Eur.J Pharm Biopharm, 2004, (57): 427.
[2]	Fischer D, Osburg B, Petersen H, et al. Effect of poly(ethyleneimine) molecular weight and pegylation on organ distribution and pharmacokinetics of polyplexes with oligodeoxynucleotides in mice[J]. Drug Metab Dispos,2004, (32): 983.
[3]	Mao S, Neu M, Germershaus O, et al. Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes[J]. Bioconjug Chem, 2006 ,(17) : 1209.
[4]	Kunath K, von Harpe A, Petersen H, et al. The structure of PEG-modified poly(ethylene imines) influences biodistribution and pharmacokinetics of their complexes with NF-kappaB decoy in mice[J].Pharm Res,2002, (19) : 810.
[5]	Zhang Y, Chen J, Zhang Y, et al. A novel PEGylation of chitosan nanoparticles for gene delivery[J].Biotechnol Appl Biochem, 2007 ,(46) :197.
[6]	Zhang H, Mardyani S, Chan WC, et al.Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics[J]. Biomacromolecules,2006, (7) :1568.
[7]	Kim TH, Nah JW, Cho MH, et al. Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles[J]. J Nanosci Nanotechnol,2006, (6) :2796.
[8]	Park IK, Kim TH, Park YH, et al. Galactosylated chitosan-graft-poly(ethylene glycol) as hepatocyte-targeting DNA carrier[J]. J Control Release,2001,(76): 349.
[9]	Mansouri S, Cuie Y, Winnik , et al. Characterization of folate-chitosan-DNA nanoparticles for gene therapy[J].Biomaterials,2006, (27) :2060..
[10]	Jiang H, Kwon J, Kim E, et al. Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting[J]. J Control Release, 2008, (131) :150.
[11]	Schaffer DV, Lauffenburger DA, Optimization of cell surface binding enhances efficiency and specificity of molecular conjugate gene delivery[J]. J Biol Chem,1998, (273) :28004.
[12]	Benns JM, Choi JS, Mahato RI, et al. pH sensitive cationic polymer gene delivery vehicle: N-Acpoly( L-histidine)-graft-poly(L-lysine) comb shaped polymer[J]. Bioconjug Chem,2000, (11): 637.
[13]	Li W, Nicol F, Szoka Jr FC, GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery[J]. Adv Drug Deliv Rev, 2004, (56) :967.
[14]	Wagner E, Effects of membrane-active agents in gene delivery[J].J Control Release, 1998, (53) :155.
[15]	Jones RA, Cheung CY, Black FE, et al. Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pHsensitive disruption of endosomal vesicles[J]. Biochem J, 2003, (372) :65.
[16]	Kim TH, Kim SI, Akaike T, et al. Synergistic effect of poly(ethylenimine) on the transfection efficiency of galactosylated chitosan/DNA complexes[J].J Control Release, 2005, (105) :354.
[17]	Thanou M, Florea BI, Geldof M, et al. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines[J]. Biomaterials, 2002, (23): 153.
[18]	Mao S, Shuai X, Unger F, et al. Synthesis, characterization and cytotoxicity of poly (ethylene glycol)-graft-trimethyl chitosan block copolymers[J]. Biomaterials, 2005,(26) : 6343.
[19]	Satoh T, Kano H, Nakatani M, et al. 6-Amino-6-deoxy chitosan. Sequential chemical modifications at the C-6 positions of N-phthaloylchitosan and evaluation as a gene carrier[J].Carbohydr Res,. 2006, (341) : 2406.
[20]	Park IK, Ihm JE, Park YH, et al. Galactosylated chitosan(GC)-graftpoly(vinyl pyrrolidone) (PVP) as hepatocytetargeting DNA carrier: preparation and physicochemical characterization of GCgraft-PVP/DNA complex (1) [J]. J Control Release,2003, (86) : 349.
[21]	Wong K, Sun G, Zhang X, et al. PEI-g-chitosan, a novel gene delivery system with transfection efficiency comparable to polyethylenimine in vitro and after liver administration in vivo[J].Bioconjug Chem,2006, (17) : 152.
[22]	Kurisawa M, Yokoyama M, Okano T, Transfection efficiency increases by incorporating hydrophobicmonomer units into polymeric gene carriers[J].J Control Release,2000, (68) : 1.
[23]	Kim YH, Gihm SH, Park CR, et al. Structural characteristics of size-controlled self aggregates of deoxycholic acidmodified chitosan and their application as a DNA delivery carrier[J].Bioconjugate Chem,2001 ,(12) : 932.
[24]	Liu WG, Zhang X, Sun SJ, et al. N-alkylated chitosan as a potential nonviral vector for gene transfection[J]. Bioconjugate Chem,2003, (14) : 782.
[25]	Hu F, Zhao M, Yuan H, et al. A novel chitosan oligosaccharidestearic acid micelles for gene delivery: properties and in vitro transfection studies[J]. Int J Pharm,2006,(315) : 158.
[26]	Mao Z, Ma L, Yan J, et al. The gene transfection efficiency of thermoresponsive N, N, N-trimethyl chitosan chloride-g-poly(N-isopropylacrylamide) copolymer[J]. Biomaterials,2007, (28) : 4488.

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Research progress of chitosan derivatives as gene delivery vector

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通讯作者: 陈斌, bchen63@163.com

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