半纤维素基pH响应性水凝胶的制备及其药物控释研究
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摘要
以从玉米芯中提取的水不溶性半纤维素(wis-AGX)(中性单糖组成为:83. 09%木糖、10. 03%葡萄糖、4. 76%阿拉伯糖、0. 76%半乳糖)为原料,在碱性介质中与丙烯酰胺接枝共聚并适度水解,在半纤维素中引入具有pH响应性的聚丙烯酸(PAA)链段,再将共聚物与聚乙烯醇(PVA)溶液共混后以戊二醛交联制备半纤维素基水凝胶。通过核磁共振仪和傅里叶变换红外光谱仪对该水凝胶的化学结构进行表征,利用扫描电子显微镜对水凝胶的形貌特征进行表征,研究了该水凝胶在去离子水和不同pH值环境下的溶胀行为。结果表明,水凝胶具有明显的pH响应性,且在pH值10时溶胀率最高,可达1210%。此外,水凝胶的溶胀率与羧基含量正相关,与戊二醛用量负相关。以茶碱作为模型药物,探讨了其在模拟胃液(pH值1. 2)和肠液(pH值7. 4)介质中的药物释放行为。在6 h内,担载药物后的水凝胶在模拟肠液中的药物累积释放量可达68%,明显高于其在胃液中51%的药物累积释放量,故此水凝胶有明显的药物缓释作用。
A kind of novel pH-sensitive hemicelluloses-based hydrogels was synthesized from the water insoluble hemicelluloses( wisAGX)( the composition of neutral monosaccharide was 83. 09% xylose,10. 03% glucose,4. 76% arabinose and 0. 76% galactose) extracted from corncobs via sequential graft copolymerization,saponification hydrolysis in alkaline medium,blending with polyvinyl alcohol( PVA) and crosslinkage in presence of glutaraldehyde. The chemical structure of the composite hydrogel was characterized by NMR and Fourier transform infrared spectroscopy,and the morphological characteristics of the hydrogel were characterized by scanning electron microscopy. The swelling properties of the hydrogels in distilled water and buffer solutions with different pH values were studied,respectively. The results show that the hydrogel has obvious pH sensitivity,and the swelling rate is the highest at pH = 10,up to 1210%. In addition,the swelling rate of the hydrogel is positively correlated with the content of —COOH and negatively correlated with the amount of glutaraldehyde. Using theophylline as a model drug,its drug release behavior in simulated gastric fluid( pH = 1. 2) and intestinal fluid( p H =7. 4) was investigated. Within 6 h,the cumulative release of the drug-loaded gel in the simulated intestinal fluid was up to 68%,which was significantly higher than the cumulative release of 51% of the drug in the gastric juice,so hydrogel has obvious drug sustained release effect and p H sensitivity.
A kind of novel pH-sensitive hemicelluloses-based hydrogels was synthesized from the water insoluble hemicelluloses( wisAGX)( the composition of neutral monosaccharide was 83. 09% xylose,10. 03% glucose,4. 76% arabinose and 0. 76% galactose) extracted from corncobs via sequential graft copolymerization,saponification hydrolysis in alkaline medium,blending with polyvinyl alcohol( PVA) and crosslinkage in presence of glutaraldehyde. The chemical structure of the composite hydrogel was characterized by NMR and Fourier transform infrared spectroscopy,and the morphological characteristics of the hydrogel were characterized by scanning electron microscopy. The swelling properties of the hydrogels in distilled water and buffer solutions with different pH values were studied,respectively. The results show that the hydrogel has obvious pH sensitivity,and the swelling rate is the highest at pH = 10,up to 1210%. In addition,the swelling rate of the hydrogel is positively correlated with the content of —COOH and negatively correlated with the amount of glutaraldehyde. Using theophylline as a model drug,its drug release behavior in simulated gastric fluid( pH = 1. 2) and intestinal fluid( p H =7. 4) was investigated. Within 6 h,the cumulative release of the drug-loaded gel in the simulated intestinal fluid was up to 68%,which was significantly higher than the cumulative release of 51% of the drug in the gastric juice,so hydrogel has obvious drug sustained release effect and p H sensitivity.
引文
[1]Kim S J,Shin S R,Shin D I,et al.Synthesis and characteristics of semi-interpenetrating polymer network hydrogels based on chitosan and poly(hydroxy ethyl methacrylate)[J].Journal of Applied Polymer Science,2010,96(1):86.
[2]Qiu Y,Park K.Environment-sensitive hydrogels for drug delivery[J].Advanced Drug Delivery Reviews,2012,64(3):49.
[3]Gupta P,Vermani K,Garg S.Hydrogels:from controlled release to p H-responsive drug delivery[J].Drug Discovery Today,2002,7(10):569.
[4]Hu X,Wei W,Qi X,et al.Preparation and characterization of a novel p H-sensitive Salecan-g-poly(acrylic acid)hydrogel for controlled release of doxorubicin[J].Journal of Materials Chemistry B,2015,3(13):2685.
[5]Zhao Yuqiang,Zhang Zhibin,Liu Ning,et al.Application of intelligent hydrogels[J].Modern Chemical Industry,2007,27(3):66.赵玉强,张志斌,刘宁,等.智能水凝胶的应用[J].现代化工,2007,27(3):66.
[6]Nasri-Nasrabadi B,Mehrasa M,Rafienia M,et al.Porous starch/cellulose nanofibers composite prepared by salt leaching technique for tissue engineering[J].Carbohydrate Polymers,2014,108(20):232.
[7]Hoare T R,Kohane D S.Hydrogels in drug delivery:Progress and challenges[J].Polymer,2008,49(8):1993.
[8]Chan A W,Whitney R A,Neufeld R J.Semisynthesis of a controlled stimuli-responsive alginate hydrogel[J].Biomacromolecules,2009,10(3):609.
[9]Saha B C.Hemicellulose bioconversion[J].Journal of Industrial Microbiology&Biotechnology,2003,30(5):279.
[10]LIN Da,PENG Hong,YU Ziping,et al.Research Progress in Separation and Purification of Hemicellulose[J].China Pulp&Paper,2011,30(1):60.林妲,彭红,余紫苹,等.半纤维素分离纯化研究进展[J].中国造纸,2011,30(1):60.
[11]EbringerováA,HromádkováZ,Heinze T.Hemicellulose[J].Polysaccharides I,2005:1.
[12]WANG An,BI Jiajie,LI Haiming.Research on Variations of Cellulose and Hemicellulose in Acid Catalytic Pre-hydrolysis of Corn Stalk[J].China Pulp&Paper,2016,35(4):6.王安,毕佳捷,李海明.玉米秸秆酸催化预水解过程中纤维素和半纤维素变化规律研究[J].中国造纸,2016,35(4):6.
[13]Sun X F,Wang H H,Jing Z X,et al.Hemicellulose-based p H-sensitive and biodegradable hydrogel for controlled drug delivery[J].Carbohydrate Polymers,2013,92(2):1357.
[14]Peng X W,Ren J L,Zhong L X,et al.Xylan-rich hemicellulosesgraft-acrylic acid ionic hydrogels with rapid responses to p H,salt,and organic solvents[J].Journal of Agricultural&Food Chemistry,2011,59(15):8208.
[15]Peng F,Guan Y,Zhang B,et al.Synthesis and properties of hemicelluloses-based semi-IPN hydrogels[J].International Journal of Biological Macromolecules,2014,65(5):564.
[16]Fang Ju.Isolation of Hemicelluloses from Corncob and Sythesize of Hemicelluloses-based Hydrogel[D].Guangzhou:South China University of Technology,2012.方驹.玉米芯半纤维素的分离及其水凝胶的制备[D].广州:华南理工大学,2012.
[17]Hebeish A,Bayazeed A,El Alfy E,et al.Synthesis and Properties of Polyacrylamide-Starch Graft Copolymers[J].Starch-Starke,2010,40(6):223.
[18]Karaaslan A M,Tshabalala M A,Buschlediller G.Wood hemicellulose/chitosan-based semi-interpenetrating network hydrogels:mechanical,swelling and controlled drug release properties[J].Bioresources,2010,5(2):1036.
[19]Xu Feng,Sun Run Cang,Zhai Mei Zhi,et al.Fractional Separation of Hemicelluloses and Lignin in High Yield and Purity from Mild Ball-Milled Periplocasepium[J].Separation Science&Technology,2008,43(11/12):3351.
[20]Nayak B R,Singh R P.Development of graft copolymer flocculating agents based on hydroxypropyl guar gum and acrylamide[J].Journal of Applied Polymer Science,2010,81(7):1776.
[21]Song Y,Zhou J,Zhang L,et al.Homogenous modification of cellulose with acrylamide in Na OH/urea aqueous solutions[J].Carbohydrate Polymers,2008,73(1):18.
[22]Tanodekaew S,Channasanon S,Uppanan P.Xylan/polyvinyl alcohol blend and its performance as hydrogel[J].Journal of Applied Polymer Science,2010,100(3):1914.
[23]Soppimath K S,Kulkarni A R,Aminabhavi T M.Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as p H-sensitive drug delivery systems:preparation and characterization[J].Journal of Controlled Release,2001,75(3):331.
[24]Mahdavinia G R,Pourjavadia A,Zohuriaan M J.Modified chitosan4.Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide)grafted chitosan with salt-and p H-responsiveness properties[J].European Polymer Journal,2004,40(7):1399.
[25]Yin Y,Ji X,Dong H,et al.Study of the swelling dynamics with overshooting effect of hydrogels based on sodium alginate-acrylic acid[J].Carbohydrate Polymers,2008,71(4):682.
[2]Qiu Y,Park K.Environment-sensitive hydrogels for drug delivery[J].Advanced Drug Delivery Reviews,2012,64(3):49.
[3]Gupta P,Vermani K,Garg S.Hydrogels:from controlled release to p H-responsive drug delivery[J].Drug Discovery Today,2002,7(10):569.
[4]Hu X,Wei W,Qi X,et al.Preparation and characterization of a novel p H-sensitive Salecan-g-poly(acrylic acid)hydrogel for controlled release of doxorubicin[J].Journal of Materials Chemistry B,2015,3(13):2685.
[5]Zhao Yuqiang,Zhang Zhibin,Liu Ning,et al.Application of intelligent hydrogels[J].Modern Chemical Industry,2007,27(3):66.赵玉强,张志斌,刘宁,等.智能水凝胶的应用[J].现代化工,2007,27(3):66.
[6]Nasri-Nasrabadi B,Mehrasa M,Rafienia M,et al.Porous starch/cellulose nanofibers composite prepared by salt leaching technique for tissue engineering[J].Carbohydrate Polymers,2014,108(20):232.
[7]Hoare T R,Kohane D S.Hydrogels in drug delivery:Progress and challenges[J].Polymer,2008,49(8):1993.
[8]Chan A W,Whitney R A,Neufeld R J.Semisynthesis of a controlled stimuli-responsive alginate hydrogel[J].Biomacromolecules,2009,10(3):609.
[9]Saha B C.Hemicellulose bioconversion[J].Journal of Industrial Microbiology&Biotechnology,2003,30(5):279.
[10]LIN Da,PENG Hong,YU Ziping,et al.Research Progress in Separation and Purification of Hemicellulose[J].China Pulp&Paper,2011,30(1):60.林妲,彭红,余紫苹,等.半纤维素分离纯化研究进展[J].中国造纸,2011,30(1):60.
[11]EbringerováA,HromádkováZ,Heinze T.Hemicellulose[J].Polysaccharides I,2005:1.
[12]WANG An,BI Jiajie,LI Haiming.Research on Variations of Cellulose and Hemicellulose in Acid Catalytic Pre-hydrolysis of Corn Stalk[J].China Pulp&Paper,2016,35(4):6.王安,毕佳捷,李海明.玉米秸秆酸催化预水解过程中纤维素和半纤维素变化规律研究[J].中国造纸,2016,35(4):6.
[13]Sun X F,Wang H H,Jing Z X,et al.Hemicellulose-based p H-sensitive and biodegradable hydrogel for controlled drug delivery[J].Carbohydrate Polymers,2013,92(2):1357.
[14]Peng X W,Ren J L,Zhong L X,et al.Xylan-rich hemicellulosesgraft-acrylic acid ionic hydrogels with rapid responses to p H,salt,and organic solvents[J].Journal of Agricultural&Food Chemistry,2011,59(15):8208.
[15]Peng F,Guan Y,Zhang B,et al.Synthesis and properties of hemicelluloses-based semi-IPN hydrogels[J].International Journal of Biological Macromolecules,2014,65(5):564.
[16]Fang Ju.Isolation of Hemicelluloses from Corncob and Sythesize of Hemicelluloses-based Hydrogel[D].Guangzhou:South China University of Technology,2012.方驹.玉米芯半纤维素的分离及其水凝胶的制备[D].广州:华南理工大学,2012.
[17]Hebeish A,Bayazeed A,El Alfy E,et al.Synthesis and Properties of Polyacrylamide-Starch Graft Copolymers[J].Starch-Starke,2010,40(6):223.
[18]Karaaslan A M,Tshabalala M A,Buschlediller G.Wood hemicellulose/chitosan-based semi-interpenetrating network hydrogels:mechanical,swelling and controlled drug release properties[J].Bioresources,2010,5(2):1036.
[19]Xu Feng,Sun Run Cang,Zhai Mei Zhi,et al.Fractional Separation of Hemicelluloses and Lignin in High Yield and Purity from Mild Ball-Milled Periplocasepium[J].Separation Science&Technology,2008,43(11/12):3351.
[20]Nayak B R,Singh R P.Development of graft copolymer flocculating agents based on hydroxypropyl guar gum and acrylamide[J].Journal of Applied Polymer Science,2010,81(7):1776.
[21]Song Y,Zhou J,Zhang L,et al.Homogenous modification of cellulose with acrylamide in Na OH/urea aqueous solutions[J].Carbohydrate Polymers,2008,73(1):18.
[22]Tanodekaew S,Channasanon S,Uppanan P.Xylan/polyvinyl alcohol blend and its performance as hydrogel[J].Journal of Applied Polymer Science,2010,100(3):1914.
[23]Soppimath K S,Kulkarni A R,Aminabhavi T M.Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as p H-sensitive drug delivery systems:preparation and characterization[J].Journal of Controlled Release,2001,75(3):331.
[24]Mahdavinia G R,Pourjavadia A,Zohuriaan M J.Modified chitosan4.Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide)grafted chitosan with salt-and p H-responsiveness properties[J].European Polymer Journal,2004,40(7):1399.
[25]Yin Y,Ji X,Dong H,et al.Study of the swelling dynamics with overshooting effect of hydrogels based on sodium alginate-acrylic acid[J].Carbohydrate Polymers,2008,71(4):682.