用于药物载体系统的多糖材料的修饰方法
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摘要
癌症是一种致死率极高的全球性疾病。迄今为止,化学药物疗法仍然是治疗癌症最为直接有效的手段,然而,目前采用的化疗药物通常不具备特异性,在杀死肿瘤细胞的同时也会对正常组织细胞带来严重的毒副作用。因此,如何安全有效地将抗癌药物输送至肿瘤组织并增强药物在肿瘤细胞内的吸收是当今癌症治疗领域急需解决的难题。药物控制释放技术通过功能化载体材料对药物进行负载,对药物释放位点及速率进行控制,从而实现降低药物毒副作用、提高药物生物利用度的目的。载体材料是实现药物控制释放的技术关键,因此,设计并开发多功能药物载体已成为该领域的研究热点。理想的药物载体通常需具备高稳定性、低生物毒性、非免疫原性及组织靶向性等特点。目前,无机纳米粒子、脂质体、水凝胶、聚合物胶束、微囊等多种药物载体已被广泛应用于癌症的诊断及治疗研究。基于天然高分子材料的药物载体因具有优良的生物相容性及临床应用前景受到了众多研究者的青睐,因此,对天然高分子材料进行化学修饰构建药物载体也已成为药物控释领域的重要研究方向。多糖是一类具有良好生物降解性及生物相容性的天然高分子材料,具有在自然界中种类丰富、水溶性高、容易进行化学修饰等优点。多糖的分子结构中含有大量的活性反应基团(羟基、氨基和羧酸基团等),经过特定的化学修饰,改变其物理或化学性质可形成水凝胶、胶束、囊泡等结构,其作为药物载体在生物材料领域具有潜在的应用价值。目前,常用的多糖修饰方法包括疏水性分子接枝、醛基化改性、原位二硫键修饰等。修饰后形成的基于多糖的药物载体具有药物释放速度可控、生物安全性好等特性,并且可以实现改变药物进入人体的方式及在体内的分布,被动或主动靶向将药物输送到特定的作用部位,达到靶向治疗的目的。本文综述了多种对天然多糖进行化学修饰,构建水凝胶、胶束及囊泡类多糖药物载体的方法,并简要讨论了基于多糖的药物载体在生物医学领域的研究前景及应用价值。
Cancer is a global disease with a leading mortality rate. To date,chemotherapy is still generally recognized as the most effective means for treating cancer which is wildly used over the world. Nevertheless,currently used chemotherapeutic drugs suffer from serious toxic side effects on normal tissue cells while killing tumor cells,due to the lack of tissue specificity. Therefore,how to safely and effectively deliver anticancer drugs to tumor tissues with enhanced drug absorption in tumor cells is an urgent problem to be solved in the field of cancer treatment. Fortunately,a promising cancer treatment technology,controlled drug release,has grabbed numerous attentions. The core idea of this technology is that drugs are loaded on functional carrier and the drug release site and rate should be controlled precisely,thereby achieving the purpose of reducing drug toxicity and improving the bioavailability of the drug.The carrier material is the key to achieving the controlled release of drugs. Hence,researchers have made great efforts on design and development of multifunctional drug carriers. Generally speaking,ideal drug carriers is characterized by high stability,low biotoxicity,non-immunogenicity and tissue targeting properties. Currently,diverse drug carriers,including inorganic nanoparticles,liposomes,hydrogels,polymer micelles and microcapsules,have been widely used in the diagnosis and treatment of cancer. Especially,drug carriers based on natural polymer materials have been favored by many researchers because of their excellent biocompatibility and clinical application prospects. Chemical modification of natural polymer materials to construct drug carriers has also become a significant research direction in the field of drug controlled release.Polysaccharide is a kind of natural polymer with favorable biodegradability and biocompatibility,which possesses rich diversity in nature,high water solubility and easiness of chemical modification. There are a large number of reactive groups on molecular chains of polysaccharides,like hydroxyl(-OH),carboxyl(-COOH) and amino groups(-NH2). After specific chemical modification,polysaccharides are endowed with modified physical or chemical properties and form hydrogels,micelles,vesicles and other structures,which enable its potential application in the field of biomaterials. Presently,the commonly used modification methods of polysaccharides include hydrophobic molecules grafting,aldehyde modification and in situ disulfide bond modification. Drug carriers based on these polysaccharides derivatives exhibit favorable biosafety,controllable drug release rate and in vivo distribution. Moreover,targeted therapy can be realized by targeted drug delivery via passive or active targeting methods.In this review,a variety of modification methods for the preparation of polysaccharide-based drug carriers are introduced,and their research prospect and application potential in the field of biological medicine are briefly discussed.
Cancer is a global disease with a leading mortality rate. To date,chemotherapy is still generally recognized as the most effective means for treating cancer which is wildly used over the world. Nevertheless,currently used chemotherapeutic drugs suffer from serious toxic side effects on normal tissue cells while killing tumor cells,due to the lack of tissue specificity. Therefore,how to safely and effectively deliver anticancer drugs to tumor tissues with enhanced drug absorption in tumor cells is an urgent problem to be solved in the field of cancer treatment. Fortunately,a promising cancer treatment technology,controlled drug release,has grabbed numerous attentions. The core idea of this technology is that drugs are loaded on functional carrier and the drug release site and rate should be controlled precisely,thereby achieving the purpose of reducing drug toxicity and improving the bioavailability of the drug.The carrier material is the key to achieving the controlled release of drugs. Hence,researchers have made great efforts on design and development of multifunctional drug carriers. Generally speaking,ideal drug carriers is characterized by high stability,low biotoxicity,non-immunogenicity and tissue targeting properties. Currently,diverse drug carriers,including inorganic nanoparticles,liposomes,hydrogels,polymer micelles and microcapsules,have been widely used in the diagnosis and treatment of cancer. Especially,drug carriers based on natural polymer materials have been favored by many researchers because of their excellent biocompatibility and clinical application prospects. Chemical modification of natural polymer materials to construct drug carriers has also become a significant research direction in the field of drug controlled release.Polysaccharide is a kind of natural polymer with favorable biodegradability and biocompatibility,which possesses rich diversity in nature,high water solubility and easiness of chemical modification. There are a large number of reactive groups on molecular chains of polysaccharides,like hydroxyl(-OH),carboxyl(-COOH) and amino groups(-NH2). After specific chemical modification,polysaccharides are endowed with modified physical or chemical properties and form hydrogels,micelles,vesicles and other structures,which enable its potential application in the field of biomaterials. Presently,the commonly used modification methods of polysaccharides include hydrophobic molecules grafting,aldehyde modification and in situ disulfide bond modification. Drug carriers based on these polysaccharides derivatives exhibit favorable biosafety,controllable drug release rate and in vivo distribution. Moreover,targeted therapy can be realized by targeted drug delivery via passive or active targeting methods.In this review,a variety of modification methods for the preparation of polysaccharide-based drug carriers are introduced,and their research prospect and application potential in the field of biological medicine are briefly discussed.
引文
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34 Debele T A,Mekurai S L,Tasi H C.Materials Science&Engineering C,2016,68,964.
2 Gao N,Lyu S,Gao C,et al.Chemical Engineering Journal,2016,287,20.
3 Fassnacht M,Terzolo M,Allolio B,et al.New England Journal of Medicine,2012,366(23),2189.
4 Zhang N,Wardwell P R,Bader R A.Pharmaceutics,2013,5(2),329.
5 Alhaique F,Casadei M A,Cencetti C,et al.Journal of Drug Delivery Science&Technology,2016,32,88.
6 Garcia-Valdez O,Champagne P,Cunningham M F.Progress in Polymer Science,2017,76,151.
7 Zhang W,Tao S L,Su H Y.Functional Materials,2017,48(2),2231(in Chinese).张稳,陶森林,苏红莹,等.功能材料,2017,48(2),2231.
8 Thakur V K,Thakur M K.Journal of Cleaner Production,2014,82(22),1.
9 Zhou T,Zhu Y,Li X,et al.Progress in Materials Science,2016,83,191.
10 Morelli A,Betti M,Pippi D,et al.Carbohydrate Polymers,2016,136,1108.
11 Wolfel A,Romero M R,Igarzabal C I A.Polymer,2017,116,251.
12 Fan M,Ma Y,Tan H,et al.Materials Science&Engineering C Materials for Biological Applications,2017,71,67.
13 Hu X,Wang Y,Zhang L,et al.Carbohydrate Polymers,2017,155,242.
14 Shen Y,Li X,Huang Y,et al.Macromolecular Research,2016,24(7),602.
15 Liu H,Rong L,Wang B,et al.Carbohydrate Polymers,2017,176,299.
16 Curcio M,Diazgomez L,Cirllo G,et al.European Journal of Pharmaceutics&Biopharmaceutics,2017,117,324.
17 Atanase L I,Desbrieres J,Riess G.Progress in Polymer Science,2017,73,32.
18 Wen Y,OH J K.Macromolecular Rapid Communications,2014,35(21),1819.
19 Nouvel C,Dubois P,Dellacherie E,et al.Journal of Polymer Science Part A Polymer Chemistry,2004,42(11),2577.
20 Wang Q Y,Su H Y,Xia C C,et al.Chinese Science Bulletin,2009,54(17),2925.
21 Uhrig D,Mays J.Polymer Chemistry,2010,2(1),69.
22 Pan H,Bo J,Jie C,et al.Food Chemistry,2014,151(4),1.
23 Besheer A,Hause G,Kressler J,et al.Biomacromolecules,2007,8(2),359.
24 Yangt S,Liu T T,Lin I H.Food Chemistry,2017,228,541.
25 Su H,Liu Y,Wang D,et al.Biomaterials,2013,34(4),1193.
26 Li W.The preparation novel dextran derivatives self-aggregation micelle and application of anti-tumor drug delivery.Master’s thesis,Harbin Institute of Technology,China,2016(in Chinese).李玮.新葡聚糖衍生物自聚集胶束制备及抑瘤药载体应用研究.硕士学位论文,哈尔滨工业大学,2016.
27 Mahmood A,Bonengel S,Laffleur F,et al.Drug Development&Industrial Pharmacy,2016,42,686.
28 Mahmood A,Lanthaler M,Laffleur F,et al.Carbohydrate Polymers,2017,167,250.
29 Marianecci C,Petralito S,Rinaldi F,et al.Journal of Drug Delivery Science&Technology,2016,32,256.
30 Zhu Y,Yang B,Chen S,et al.Progress in Polymer Science,2016,64,1.
31 Zhu Y,Liu L,Du J.Macromolecules,2013,46(1),194.
32 Long L X,Yuan X B,Qian X M et al.Journal of Tianjin University(Science and Technology),2013,46(6),510(in Chinese).龙丽霞,原续波,钱小敏,等.天津大学学报(自然科学与工程技术版),2013,46(6),510.
33 Schaytz C,Louguet S,Le M J,et al.Angewandte Chemie,2009,121(14),2572.
34 Debele T A,Mekurai S L,Tasi H C.Materials Science&Engineering C,2016,68,964.