摘要
本文用滴制法制备PVA/SA/ST复合水凝胶微球,优化PVA、SA、ST的配比及交联剂CaCl_2浓度,确定其胶凝时间、干燥时间、粒径大小及分布;用SEM表征其形貌特点;用PVA/SA/ST复合水凝胶装载牛血清白蛋白、盐酸四环素类药物载药复合水凝胶微球,测定了其包封率和载药量,并对其释药性能作了研究。所得结果如下。
1.在凝胶微球的制备过程中,用4~4正交分析法得出制备凝胶微球的PVA、SA、ST、CaCl_2的最优浓度分别为14wt%、3.5wt%、8wt%、0.1M。凝胶微球最佳胶凝时间是20～25min,最佳干燥时间为90min,微球最佳分布区间在0.94～1.06mm这个区间,微球的平均直径Dav为0.998mm。
2.通过扫描电镜(SEM)的观察,发现在低放大倍数下,微球整体形态圆整,表面光滑,微球的粒径大约为1mm。
3.凝胶在模拟胃液(pH=1.4盐酸缓冲液)中几乎不溶胀;与模拟结肠液(pH=7.4PBS缓冲液)相比,微球在模拟小肠液(pH=6.8的PBS缓冲液)中的溶胀性能要小。随着温度升高,凝胶微球的溶胀度增加,可见温度对凝胶微球的溶胀性能有着较大的影响。人体体温的37℃下凝胶微球的溶胀度是凝胶微球溶胀的最佳温度。
4.微球在模拟胃液(pH=1.4盐酸缓冲液)中,在2h时微球的溶蚀达到14.5%;微球在模拟小肠液(pH=6.8PBS缓冲液)中的4个小时内微球的溶蚀达到25.6%,微球在模拟结肠液(pH=7.4PBS缓冲液)中的4个小时内微球的溶蚀达到100%,可以确定微球在经过胃、小肠到达结肠之后能够完全溶蚀。
5.载牛血清白蛋白的微球的载药量随牛血清白蛋白浓度的增加而下降,10mg/ml的载药浓度下的微球的载药量最高,达到81.1%;包封率随牛血清白蛋白浓度的增加而增加,50mg/ml的载药浓度下的微球的包封率最高,达到37.9%。
6.载盐酸四环素的微球的载药量随盐酸四环素浓度的增加而增加;载药浓度为5mg/ml的微球的载药量最高,最高为1.79%;包封率随盐酸四环素浓度的增加而减小,载药浓度为1mg/ml的微球的包封率最高,达到42%。
7.通过比较两种药物的释放,发现载牛血清白蛋白凝胶微球表现出良好的药物缓释,而模拟小肠液(pH=6.8的PBS缓冲液)和模拟结肠液(pH=7.4的PBS缓冲液)对载盐酸四环素微球的药物释放没有多大影响,从而可以推断盐酸四环素药物水凝胶的释放机理主要是扩散。
8.实验发现,在释药过程中,载药微球起到了逐步缓慢释药的效果,因而PVA/SA/ST复合水凝胶能用作口服药物的载体。
This paper has introduced the background,theory of the hydrogel,and the hydrogels PVA and SA.We have optimized the concentration of the PVA、SA、ST、CaCl_2 by the preparation ways of dropping method and detected the gelling time, drying time,particle size and distribution.We have characterized its morphological property by SEM.Then we use the blend hydrogels to load Albumin and Tetracycline,calculated the drug-loading rate and entrapment rate, and gave a study on the external-load-drug experiment.Main results were as follows:
1.In the preparation process,we get the result of the concentration of the polyvinyl alcohol,sodium alginate,starch and calcium chloride solution through Orthogonal analysis is 14wt%、3.5wt%、8wt%、0.1M,the gelling time is 20-25min,the drying time is 90min,the distribution is 0.94mm-1.06mm,and the particle size is 0.998mm
2.With the observation of SEM,the hydrogels like a round ball,has smooth surface,the size of the hydrogels is about 1mm.
3.The hydrogels in a simulated gastric juice(pH1.4 HCl buffer solution) in almost no swelling;By comparison with simulating colon solution(pH7.4 PBS buffer solution),the hydrogels beads swelled the volume bigger in simulated intestinal juice(pH6.8 PBS buffer solution).With the temperature increasing,the hydrogels swelling bigger,so the temperature has an importance to the SR of hydrogels,but the body temperature of 37℃is the best temperature.
4.We detected that,after in simulated gastric juice(2hr),the dissolution of the hydrogels reach to 14.5%.After in simulated intestinal solution(4hr),the dissolution reach to 25.6%.After in simulated colon solution(2hr),the dissolution of the hydrogels reach to 100%.By comparison with simulating gastric solution, the hydrogels bead swelled the volume bigger and released the drug faster in pH6.8 PBS and pH7.4 PBS.Through the stomach,small intestine and the colon, hydrogels can be identified completed dissolution.
5.With the concentration of BSA increased,drug loading decreased.10mg/ml of the drug-loaded hydrogels have the highest drug loading to 81.1%.With the concentration of BSA increased,encapsulation efficiency increased,50mg/ml of the drug-loaded hydrogels have the highest encapsulation efficiency,reaching 37.9%.
6.With the concentration of Tetracycline-HCl increased,drug loading increased.5mg/ml of the drug-loaded hydrogels have the highest drug loading to 1.79%.With the concentration of Tetracycline-HCl increased,encapsulation efficiency decreased,1mg/ml of the drug-loaded hydrogels have the highest encapsulation efficiency,reaching 42%.
7.By comparing the release of the two drugs,we found that hydrogels containing BSA demonstrated good drug-control-release.The simulated small intestinal juice and simulated colonic fluid have much influence on drug release in hydrogels containing Tetracycline-HCl,which may be inferred that hydrogels containing Tetracycline-HCl drug release mechanism of hydrogel mainly proliferation.Obviously this can not be as microspheres and bovine serum albumin to control drug release so effective,but also requires further study.
8.In the process,we found that the blend hydrogel have good release-control effect,so we can concludede the PVA/SA/ST blend hydrogel can be applied to the oral drug carrier.
引文
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