先辐射后冻融法制备聚乙烯醇/水溶性壳聚糖/甘油水凝胶的云南白药药物释放性能研究

INVESTIGATION OF YUNNAN BAIYAO RELEASE BEHAVIOR FROM PVA/WATER-SOLUBLE CHITOSAN/GLYCEROL HYDROGELS PREPARED BY IRRADIATION FOLLOWED BY FREEZE-THAWING

采用先辐射后冻融的方法制备了一系列聚乙烯醇(PVA)/水溶性壳聚糖/甘油水凝胶,通过浸泡法在水凝胶中载入云南白药,并且研究了溶液pH值、离子强度、冻融次数和PVA浓度对水凝胶溶胀性能和云南白药释放性能的影响.研究发现水凝胶的溶胀度随溶液离子强度的增大而下降,且酸性溶液大于中性溶液.水溶性壳聚糖的加入有利于云南白药载入凝胶,同时使云南白药的释放具有pH和离子强度敏感性.云南白药的释放量在模拟体液中最大,在中性溶液中次之,在水和酸性溶液中最小,与溶胀度变化关系相反.而水凝胶的溶胀度和云南白药释放量均随冻融次数和PVA浓度的增大而下降.分析表明,云南白药在不同介质中的释放量主要取决于药物和溶液中离子的交换能力;在相同介质中,不同凝胶的药物释放量受溶胀度影响明显.凝胶溶胀速率远大于药物释放速率说明后者主要由扩散过程控制.药物释放的pH敏感性表明该水凝胶具备用作云南白药的口服载体的潜力.

A series of poly（vinyl alcohol）/water-soluble chitosan/glycerol hydrogels were prepared by irradiation followed by freeze-thawing. Yunnan Baiyao was loaded into the hydrogels by solvent sorption technique. The influences of pH, ionic strength, freeze-thawing cycles and PVA concentration on the swelling capacity and Yunnan Baiyao release behavior were investigated. The swelling capacity decreased with increasing ionic strength, and it was larger in acidic media than in neutral media. Much more amount of Yunnan Baiyao could be loaded into PVA/wschitosan/glycerol hydrogels than into PVA hydrogels. Yunnan Baiyao release behavior of the former hydrogel showed pH and ionic strength sensitivity due to the existence of ws-chitosan. Larger amount of Yunnan Baiyao was released in pseudo-extracellular fluid solution than in neutral media and only small amount of the drug was released in acidic media and in distilled water, which was opposite to the swelling behavior. However, it was found that the swelling capacity and Yunnan Baiyao release amount both decreased with increasing freeze-thawing cycles and PVA concentration. These results indicated that Yunnan Baiyao release amount in various release media was mainly determined by the ionic exchange capacity between the drug and the ions in the solution. However, the release amount was mainly determined by swelling capacity when the hydrogels were in the same release media for different hydrogels. The swelling rate was much larger than the drug release rate indicating that the drug release rate was mainly diffusion-controlled. The pH sensitive drug release behavior indicated that the hydrogel had potential to be used for the oral delivery of Yunnan Baiyao.