高等学校化学学报
高等學校化學學報
고등학교화학학보
CHEMICAL JOURNAL OF CHINESE UNIVERSITIES
2014年
3期
652-659
,共8页
葡聚糖%牛血清白蛋白%药物释放%纳米粒子%抗肿瘤活性%阿霉素
葡聚糖%牛血清白蛋白%藥物釋放%納米粒子%抗腫瘤活性%阿黴素
포취당%우혈청백단백%약물석방%납미입자%항종류활성%아매소
Dextran%Bovine Sercurn albumin ( BSA )%Drug delivery%Nanoparticles%Anticancer activity%Doxorubicin
以Maillard反应制备的牛血清白蛋白-葡聚糖共价接枝物作为载体,通过调节混合溶液的pH值和温度制备负载阿霉素的白蛋白-葡聚糖纳米粒子.利用分子量为5×103,10×103和62×103的葡聚糖制备了多种共价接枝物,研究了共价接枝物分子量对载药纳米粒子的粒径和稳定性及载药量的影响.用短链葡聚糖(分子量5×103和10×103)制备的纳米粒子粒径为60 nm左右,用长链葡聚糖(分子量62×103)制备的纳米粒子粒径约为200 nm；阿霉素的包埋效率为81%~98%,包埋量为7.4%~16.9%.细胞实验结果表明,共价接枝物具有很好的生物相容性；与自由阿霉素相比,纳米粒子可以促进阿霉素进入人口腔上皮癌细胞；受缓释性质的影响,纳米粒子在低浓度时的细胞毒性要小于自由阿霉素.与长链葡聚糖纳米粒子相比,接枝度高的短链葡聚糖纳米粒子由于具有较小的粒径、密集的葡聚糖分子刷表面、一定的自由阿霉素浓度和较快的阿霉素释放速率,因而更容易进入细胞并具有更好的体外抗肿瘤活性.
以Maillard反應製備的牛血清白蛋白-葡聚糖共價接枝物作為載體,通過調節混閤溶液的pH值和溫度製備負載阿黴素的白蛋白-葡聚糖納米粒子.利用分子量為5×103,10×103和62×103的葡聚糖製備瞭多種共價接枝物,研究瞭共價接枝物分子量對載藥納米粒子的粒徑和穩定性及載藥量的影響.用短鏈葡聚糖(分子量5×103和10×103)製備的納米粒子粒徑為60 nm左右,用長鏈葡聚糖(分子量62×103)製備的納米粒子粒徑約為200 nm；阿黴素的包埋效率為81%~98%,包埋量為7.4%~16.9%.細胞實驗結果錶明,共價接枝物具有很好的生物相容性；與自由阿黴素相比,納米粒子可以促進阿黴素進入人口腔上皮癌細胞；受緩釋性質的影響,納米粒子在低濃度時的細胞毒性要小于自由阿黴素.與長鏈葡聚糖納米粒子相比,接枝度高的短鏈葡聚糖納米粒子由于具有較小的粒徑、密集的葡聚糖分子刷錶麵、一定的自由阿黴素濃度和較快的阿黴素釋放速率,因而更容易進入細胞併具有更好的體外抗腫瘤活性.
이Maillard반응제비적우혈청백단백-포취당공개접지물작위재체,통과조절혼합용액적pH치화온도제비부재아매소적백단백-포취당납미입자.이용분자량위5×103,10×103화62×103적포취당제비료다충공개접지물,연구료공개접지물분자량대재약납미입자적립경화은정성급재약량적영향.용단련포취당(분자량5×103화10×103)제비적납미입자립경위60 nm좌우,용장련포취당(분자량62×103)제비적납미입자립경약위200 nm；아매소적포매효솔위81%~98%,포매량위7.4%~16.9%.세포실험결과표명,공개접지물구유흔호적생물상용성；여자유아매소상비,납미입자가이촉진아매소진입인구강상피암세포；수완석성질적영향,납미입자재저농도시적세포독성요소우자유아매소.여장련포취당납미입자상비,접지도고적단련포취당납미입자유우구유교소적립경、밀집적포취당분자쇄표면、일정적자유아매소농도화교쾌적아매소석방속솔,인이경용역진입세포병구유경호적체외항종류활성.
Bovine Sercurn albumin-dextran( BSA-dextran) conjugates were prepared with different molecular weights of dextran and different molar ratios of BSA to dextran via Maillard reaction. Doxorubicin loaded BSA-dextran nanoparticles were fabricated by changing the pH and then temperature of the mixture. The nanoparti-cles with 5í103 and 10í103 dextran have a size about 60 nm, and the nanoparticles with 62í103 dextran have a size about 200 nm. The doxorubicin loading efficiency is in the range of 81%-98%, and the loading amount is 7.4%-16.9%. In vitro cell viability investigation confirms the excellent biocompatibility of BSA-dextran conjugates. Compared with free doxorubicin, the nanoparticles can enhance the cellular internalization of the loaded doxorubicin and they show lower anticancer activity at lower doxorubicin concentrations because of the slower release of the loaded doxorubicin. In comparison with the nanoparticles with 62í103 and 10í103 dextran, the nanoparticles with 5í103 dextran and higher dextran conjugation degree show better cellular inter-nalization and better anticancer activity in vitro due to their smaller size, denser dextran brush surface, certain free doxorubicin concentration, and faster release rate of the loaded doxorubicin.
