乙二醇壳聚糖接枝羧甲基β-环糊精用于运载疏水性抗癌药物甲氨蝶呤

doi:10.7523/j.issn.1002-1175.2013.02.009

中国科学院大学学报 ›› 2013, Vol. 30 ›› Issue (2): 200-205.DOI: 10.7523/j.issn.1002-1175.2013.02.009

乙二醇壳聚糖接枝羧甲基β-环糊精用于运载疏水性抗癌药物甲氨蝶呤

谭海娜¹, 姚鑫^1,2

1. 中国科学院研究生院化学与化学工程学院, 北京 100049;
2. 北京大学天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2012-03-09 修回日期:2012-04-11 发布日期:2013-03-15
通讯作者: 姚鑫
基金资助:
国家自然科学基金(20877097)、中国科学院研究生院院长基金(Y15102CN00)和天然药物及仿生药物国家重点实验室开放基金(K20120207)资助

Glycol chitosan-graft-carboxymethyl β-cyclodextrin as carrier of hydrophobic anticancer drug methotrexate

TAN Hai-Na¹, YAO Xin^1,2

1. College of Chemistry and Chemical Engineering, Graduate University, Chinese Academy of Sciences, Beijing 100049, China;
2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China

Received:2012-03-09 Revised:2012-04-11 Published:2013-03-15

摘要/Abstract

摘要：

利用简单的交联反应合成乙二醇壳聚糖接枝羧甲基β-环糊精(GCH-g-CM β-CD),通过红外光谱、核磁共振谱和浓硫酸-苯酚降解法对其进行表征.将GCH-g-CM β-CD用于运载疏水性抗癌药物甲氨蝶呤(MTX),应用表面等离子体激元共振仪在线原位监测其与MTX的结合,紫外吸收分光光度法测定主客体分子的结合比为1:1.证明GCH-g-CM β-CD通过CM β-CD的疏水空腔与MTX结合,形成稳定的水溶性复合物.因此,GCH-g-CM β-CD有望用于疏水性抗肿瘤药物的运载.

关键词: 乙二醇壳聚糖接枝羧甲基β-环糊精, 药物载体, 抗癌药物, 甲氨蝶呤, 表面等离子体激元共振仪

Abstract:

Glycol chitosan-graft-carboxymethyl β-cyclodextrin (GCH-g-CM β-CD) was synthesized by a simple cross-linking reaction, and the products were characterized by FT-IR,¹³C-NMR, and H₂SO₄-phenol degradation method. Interaction between GCH-g-CM β-CD and hydrophobic anticancer drug methotrexate (MTX) was studied by surface plasmon resonance (SPR) in real time and in situ. UV-vis spectroscopy analysis indicated that each CM β-CD unit binds one MTX molecule, which showed that MTX can be successfully loaded into the hydrophobic cavities of grafted CM β-CDs. The results indicated that the newly synthesized GCH-g-CM β-CD can be used as hydrophobic anticancer drug carrier.

Key words: glycol chitosan-graft-carboxymethyl β-cyclodextrin, drug carrier, anticancer drug, methotrexate, surface plasmon resonance

中图分类号:

O657

谭海娜, 姚鑫. 乙二醇壳聚糖接枝羧甲基β-环糊精用于运载疏水性抗癌药物甲氨蝶呤[J]. 中国科学院大学学报, 2013, 30(2): 200-205.

TAN Hai-Na, YAO Xin. Glycol chitosan-graft-carboxymethyl β-cyclodextrin as carrier of hydrophobic anticancer drug methotrexate[J]. , 2013, 30(2): 200-205.

参考文献

[1] Fung S Y, Yang H, Bhola P T, et al. Self-assembling peptide as a potential carrier for hydrophobic anticancer drug ellipticine: complexation, release and in vitro delivery[J]. Advanced Functional Materials, 2009, 19(1):74-83.

[2] Yue Z G, Wei W, You Z X, et al. Iron oxide nanotubes for magnetically guided delivery and pH-activated release of insoluble anticancer drugs[J]. Advanced Functional Materials, 2011, 21(18):3446-3453.

[3] Chen D Y, Xia X W, Gu H W, et al. pH-responsive polymeric carrier encapsulated magnetic nanoparticles for cancer targeted imaging and delivery[J]. Journal of Materials Chemistry, 2011, 21(34):12682-12690.

[4] Mao H Q, Roy K, Troung-Le V L, et al. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency[J]. Journal of Controlled Release, 2001, 70(3):399-421.

[5] Amidi M, Mastrobattista E, Jiskoot W, et al. Chitosan-based delivery systems for protein therapeutics and antigens[J]. Advanced Drug Delivery Reviews, 2010, 62(1):59-82.

[6] van der Lubben I M, Verhoef J C, Borchard G, et al. Chitosan for mucosal vaccination[J]. Advanced Drug Delivery Reviews, 2001, 52(2):139-144.

[7] Zhou H F, Yu W T, Guo X, et al. Synthesis and characterization of amphiphilic glycidol-chitosan-deoxycholic acid nanoparticles as a drug carrier for doxorubicin[J]. Biomacromolecules, 2010, 11(12):3480-3486.

[8] Hua D B, Jiang J L, Kuang L J, et al. Smart chitosan-based stimuli-responsive nanocarriers for the controlled delivery of hydrophobic pharmaceuticals[J]. Macromolecules, 2011, 44(6):1298-1302.

[9] Uekama K, Hirayama F, Irie T. Cyclodextrin drug carrier systems[J]. Chemical Reviews, 1998, 98(5):2045-2076.

[10] Wolf L K, Gao Y, Georgiadis R M. Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements[J]. Journal of the American Chemical Society, 2007, 129(34):10503-10511.

[11] Krauland A H, Alonso M J. Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system[J]. International Journal of Pharmaceutics, 2007, 340(1/2):134-142.

[12] Prabaharan M, Mano J F. Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug[J]. Macromolecular Bioscience, 2005, 5(10):965-973.

[13] Smith E A, Thomas W D, Kiessling L L, et al. Surface plasmon resonance imaging studies of protein-carbohydrate interactions[J]. Journal of the American Chemical Society, 2003, 125(20):6140-6148.

[14] Luan Q F, Zhou K B, Tan H N, et al. Au-NPs enhanced SPR biosensor based on hairpin DNA without the effect of nonspecific adsorption[J]. Biosensors & Bioelectronics, 2011, 26(5):2473-2477.

[15] Kolomenskii A A, Gershon P D, Schuessler H A. Sensitivity and detection limit of concentration and adsorption measurements by laser-induced surface-plasmon resonance[J]. Applied Optics, 1997, 36(25):6539-6547.

[16] Song Q D, Ding Y, Li X M, et al. Synthesis of carboxymethyl-β-cyclodextrin and its hemolysis and solubilization[J]. Journal of Shandong University:Health Sciences, 2005, 43(2):166-169 (in Chinese).宋全道,丁易,李新民,等. 羧甲基-β-环糊精的溶血作用及对槲皮素的增溶作用[J]. 山东大学学报:医学版,2005,43(2):166-169.

[17] Dubois M, Gilles K A, Hamilton J K, et al. Colorimetric method for determination of sugars and related substances[J]. Analytical Chemistry, 1956, 28(3):350-356.

[18] Chayed S, Winnik F M. In vitro evaluation of the mucoadhesive properties of polysaccharide-based nanoparticulate oral drug delivery systems[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 65(3):363-370.

[19] Kobayashi H, Endo T, Ogawa N, et al. Evaluation of the interaction between beta-cyclodextrin and psychotropic drugs by surface plasmon resonance assay with a Biacore (R) system[J]. Journal of Pharmaceutical and Biomedical Analysis, 2011, 54(1):258-263.

[20] Stancanelli R, Ficarra R, Cannava C, et al. UV-vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-beta-cyclodextrin inclusion complex[J]. Journal of Pharmaceutical and Biomedical Analysis, 2008, 47(4-5):704-709.

乙二醇壳聚糖接枝羧甲基β-环糊精用于运载疏水性抗癌药物甲氨蝶呤

Glycol chitosan-graft-carboxymethyl β-cyclodextrin as carrier of hydrophobic anticancer drug methotrexate

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