细菌纤维素/胶原蛋白多孔微球的制备及性能
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摘要
利用Malaprade反应原理,以高碘酸钠为氧化剂,对细菌纤维素(Bacterial cellulose,BC)进行氧化,制备2,3-二醛细菌纤维素(2,3-dialdehyde bacteria cellulose,DABC).利用希夫碱反应使DABC中的-CHO-与胶原蛋白(collagen,COL)中的-NH2反应,制备CDABC复合材料.采用反相悬浮再生法将CDABC制备成BC/COL多孔微球.以BC/COL多孔微球载药率为指标,采用单因素及正交实验研究CDABC质量分数、十六烷/(CDABC/IL)比例、乳化时间及乳化温度等因素对微球制备影响.利用FT-IR、XRD、TG及SEM对BC、DABC、CDABC、BC/COL多孔微球的化学基团、结晶度、热性能及表面形貌进行分析.结果表明:BC/COL多孔微球制备最优工艺为:乳化温度35℃,乳化时间5h,十六烷∶(CDABC/IL)=10∶1,CDABC质量分数4%.在此工艺下制备BC/COL多孔微球载药率为254 mg/g.FT-IR、XRD、TG及SEM检测结果表明,BC氧化、CDABC复合均能成功进行,且复合作用对材料的形貌、结晶度及热性能均有一定改善作用.采用反相悬浮再生法能够成功制备BC/COL多孔微球,可为后续药物的负载提供条件.
In this study,Bacterial cellulose(BC)was oxidized to 2,3-dialdehyde bacteria cellulose(DABC)through Malaprade reaction.Then BC/COL composite materials(CDABC)was prepared by DABC and collagen(COL)through schiff's base reaction.And BC/COL porous microspheres was prepared with CDABC by reversed-phase suspension regeneration method.During which,with drug-loading rate as an index,CDABC mass fraction,hexadecane/(CDABC/IL)ratio,emulsifying time and temperature were optimized using single factor and orthogonal experiments.The chemical groups,crystallinity,thermal properties and surface morphology of BC,DABC,CDABC,BC/COL porous microspheres were analyzed by FT-IR,XRD,TG and SEM respectively.The results showed that the optimal preparing process of BC/COL porous microspheres was determined as follows:CDABC mass fraction was 4%,hexadecane/(CDABC/IL)ratio was 10∶1,emulsifying time was 5 hand emulsifying temperature was 35 ℃.FT-IR,XRD,TG and SEM results showed that both BC oxidation and CDABC preparation can be successfully carried out,and the morphology,crystallinity and thermal properties of materials can be improved through composition.BC/COL porous microspheres can be prepared successfully by reversed-phase suspension regeneration method,which can provide conditions for subsequent drug loading.
In this study,Bacterial cellulose(BC)was oxidized to 2,3-dialdehyde bacteria cellulose(DABC)through Malaprade reaction.Then BC/COL composite materials(CDABC)was prepared by DABC and collagen(COL)through schiff's base reaction.And BC/COL porous microspheres was prepared with CDABC by reversed-phase suspension regeneration method.During which,with drug-loading rate as an index,CDABC mass fraction,hexadecane/(CDABC/IL)ratio,emulsifying time and temperature were optimized using single factor and orthogonal experiments.The chemical groups,crystallinity,thermal properties and surface morphology of BC,DABC,CDABC,BC/COL porous microspheres were analyzed by FT-IR,XRD,TG and SEM respectively.The results showed that the optimal preparing process of BC/COL porous microspheres was determined as follows:CDABC mass fraction was 4%,hexadecane/(CDABC/IL)ratio was 10∶1,emulsifying time was 5 hand emulsifying temperature was 35 ℃.FT-IR,XRD,TG and SEM results showed that both BC oxidation and CDABC preparation can be successfully carried out,and the morphology,crystallinity and thermal properties of materials can be improved through composition.BC/COL porous microspheres can be prepared successfully by reversed-phase suspension regeneration method,which can provide conditions for subsequent drug loading.
引文
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[3]Kaushai S,Amiei G E,Guiesrian K J,et al.Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo[J].Nature Medicine,2001,7(9):1 035-1 040.
[4]杨晓霞,奕玉霞,蔡晓青,等.多孔微球在医药领域的应用[J].药物生物技术,2011,18(5):449-452.
[5]张启英,张天柱,胡克,等.多孔微球在三维细胞培养中的研究进展[J].东南大学学报(医学版),2013,32(1):90-94.
[6]Malda J,Frondoza C G.Micro-carriers in the engineering of cartilage and bone[J].Trends Biotechnol,2006,24(7):299-304.
[7]刘国诠.生物工程下游技术[M].北京:化学工业出版社,2003.
[8]文建川,姚晋荣,邵正中.非生理活性蛋白质的研究进展及其在材料领域中的应用[J].高分子学报,2011(1):12-23.
[9]Dugan J M,Gough J E,Eichhorn S J.Bacterial cellulose scaffolds and cellulose nanowhiskers for tissue engineering[J].Nano Medicine(Lond),2013,8(2):287-298.
[10]Esguerra M,Fink H,Laschke M W,et al.Intravital fluorescent microscopic evaluation of bacterial cellulose as scaffold for vascular grafts[J].Journal of Biomedical Materials Research Part A,2010,93(1):140-149.
[11]李扬,沈建成,徐枫,等.纳米细菌纤维素的细胞生物相容性[J].中国组织工程研究,2012,16(51):9 541-9 545.
[12]王宗良,贾原媛,石毅,等.纳米细菌纤维素膜的表征与生物相容性研究[J].高等学校化学学报,2009,30(8):1 553-1 558.
[13]陈艳梅,奚廷斐,郑琪,等.细菌纤维素的体内降解及其组织相容性[J].科技导报,2009,27(21):61-66.
[14]Dash R,Foston M,Ragauskas A J.Improving the mechanical and thermal properties of gelatin hydrogels cross-linked by cellulose nanowhiskers[J].Carbohydrate Polymers,2013(91):638-645.
[15]Doyle B B,Bendit E G,Blout E R.Infrared spectroscopy of collagen and collagen-like polypeptides[J].Biopolymers,1975,14(5):937-957.
[16]Pei Y,Yang J,Liu P,et al.Fabrication,properties and bioapplications of cellulose-collagen hydrolysate composite films[J].Carbohydrate Polymers,2013,92:1 752-1 760.