PVA水凝胶载体药物释放的物理化学研究
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摘要
聚乙烯醇(PVA)水凝胶因其无毒,无副作用,具有良好的弹性及生物适应性而广泛用于药物载体。为有效利用水凝胶载体于药物控制释放,本文开展PVA水凝胶载药体系的物理化学性质研究。
     1.PVA水凝胶的溶胀性和其若干物理性质研究。粘度法测定所用PVA的相对分子质量;反复冷冻—解冻法制备了物理交联PVA水凝胶;测定水凝胶的溶胀率;热重分析考察了水凝胶的含水量。结果表明:随着介质温度的升高,水凝胶的溶胀速率变快,平衡溶胀比增加。
     2.PVA装载水杨酸水凝胶药物释放速率的研究。物理法制备PVA装载水杨酸水凝胶;红外光谱考察药物和聚合物的相互作用、相容性;以水杨酸为模型药物,研究温度、药物装载量等因素对PVA水凝胶释放速率的影响;动力学模型拟合实验数据;释药机理分析。结果表明:PVA羟基与水杨酸之间氢键作用有利于两者的相容性;随着介质温度的上升,药物的释放速率增加;随着药物装载量的增加,药物的累积释放率降低;PVA水凝胶中水杨酸的释药规律符合一级释放模型。
     3.PVA载水飞蓟宾水凝胶释药速率研究。考察水飞蓟宾的若干理化性质,如水飞蓟宾药物的纯度,水飞蓟宾的熔点和熔融焓;建立了水飞蓟宾在水溶液中浓度的测定方法;物理法制备PVA装载水飞蓟宾水凝胶;测定PVA载水飞蓟宾水凝胶的释放速率及影响因素;动力学模型拟合实验数据;释药机理分析。结果表明:随着介质温度的上升,药物的释放速率增加;前期释放速率很大,从第2h至第10h释放速率大大减慢,之后达到释放平衡;动力学符合零级释放模型。
     4.PVA/明胶共混水凝胶对水杨酸药物释放的影响。考察PVA/明胶不同配比对共混水凝胶的溶胀率的影响,对水杨酸药物释放的影响;红外光谱研究明胶、PVA及水杨酸之间的相互作用;PVA/明胶配比对水杨酸药物释放的影响;动力学模型关联释放曲线,探索释放机理。结果表明:在一定范围内,PVA质量增加,共混凝胶的释药速率降低;高出此范围,PVA质量增加,释药速率增加;释药动力学符合一级释放模型。
Poly(vinyl alcohol)(PVA) hydrogel is non-toxic, non side-effect, with good elasticityand biocompatibility. They have been used extensively as a drug release carrier. In order touse hydrogel as drug carrier for controlled release effectively, we studied thephysical-chemistry properties for the process of drug release from PVA hydrogel. There are4 parts in this work.
     1. Study on the swelling ratio of PVA hydrogels and its other physical properties. Therelative molecular weight of PVA is calculated by measuring the viscosity of its aqueoussolution. PVA hydrogels were prepared by a physical method of repeat freezing andthawing. The swelling ratio of the hydrogels at several temperatures was determined. Thecontent of water in PVA hydrogel was determined by a TG apparatus. Experimental resultindicates that, the swelling rate and the equilibrium swelling ratio of PVA hydrogelincrease with the rise of temperature.
     2. Study on the release rate of salicylic acid from PVA hydrogel. A slice form of PVAhydrogel containing salicylic acid was prepared by physical method. The interactionbetween the drug and polymer was studied by FTIR method and the factors influencing thedrug release were investigated. Kinetic models were applied to fit the drug release data, and the release mechanism was analyzed from the model parameters. Experiment resultsindicate that, the hydrogen bonds between hydroxyl of PVA and salicylic acid leads to thecompatibility between them. The drug release rate is accelerated with the rise oftemperature and decreased with the increase of drug loadage. The fitting result suggests afirst-order kinetic equation for salicylic acid release.
     3. Study on the release rate of silybin from PVA hydrogel. Some physical and chemicalparameters such as purity, melting enthalpy of silybin and the concentration of silybin in water weremeasured, a slice form of PVA hydrogel containing silybin was prepared by physical method.The release rate of silybin from PVA hydrogel was measured, and the factors influencingdrug release were investigated. Kinetic models were applied to fit the drug release data, and the release mechanism was discussed. Experimental results indicate that, the drugrelease rate was accelerated with the increase in temperature. The release rate was large atthe beginning stage, and slowed down at the following release stage. After 10 hours,equilibrium was reached. Kinetic analysis suggests a zero-order kinetic mechanism.
     4. Study on the release rate of salicylic acid from a PVA/gelatin mixing hydrogel.The mixing hydrogel with different PVA to gelatin ratio were prepared by a physicalmethod. The effect of mixing ratio on the swelling ratio and the release rate weredetermined. The interaction between the drug and polymer was studied by a FTIR method.Kinetic equations were applied to fit the release data. Experimental results shown that, thedrug release rate is slowed down while PVA's ratio increases. However, out of acomposition limit, an opposite effect on release rate was observed. Kinetic analysissuggests a first-order kinetic mechanism for salicylic acid release from the mixinghydrogel.
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