氢化可的松琥珀酸钠结肠靶向pH敏感型水凝胶的制备及其靶向性研究

Preparation of Colon-targeting pH-Sensitive Hydrogel of Hydrocortisone Sodium Succinate and Experiment About Colon-targeting

关键词:  水凝胶  溃疡性结肠炎  氢化可的松琥珀酸钠  结肠靶向给药系统

Key words:  hydrogel  ulcerative colitis  hydrocortisone sodium succinate  colon-specific drug delivery system

摘要:

目的 制备氢化可的松琥珀酸钠（hydrocortisone sodium succinate，HSS）结肠靶向pH型水凝胶，并探讨其结肠靶向性。方法 采用单因素考察法优化HSS结肠靶向型水凝胶（colon-targeting hydrogel of hydrocortisone sodium succinate，HSS-GEL）的处方制备工艺。以魔芋葡甘聚糖（konjac glucomannan，KGM）、黄原胶（xanthan gum，XG）与海藻酸钠（sodium alginate，SA）作为水凝胶材料，HSS为模型药物，甘油为迟释剂，制备了HSS-GEL。以药物体外释放度为指标，考察了甘油及其用量、材料比例、制备温度及载药量对HSS-GEL释放度的影响，确定HSS-GEL最佳处方与制备工艺，并考察其在不同pH介质中的释放特性；通过HSS-GEL在大鼠胃、小肠、盲结肠及其内容物的匀浆的孵化实验，考察HSS-GEL在不同组织匀浆中的释药量，评价其结肠靶向性。结果 最优处方为KGM-XG-SA比例2.5：4：4，甘油用量为处方量的4%，制备温度为70℃。体外释放结果显示HSS-GEL在pH 1.2及pH 6.8的PBS溶液中的释放量总和≤ 20%，即>80%的药量能进入到pH 7.4的介质中；大鼠胃、小肠、盲结肠及其匀浆孵化实验中显示在孵化1~10 h内，盲结肠内容物中的HSS浓度均远大于胃及小肠中的药物浓度，且几乎在每个时间点都大于两者药量的总和。结论 HSS-GEL制备工艺简单、稳定，且所制备的HSS-GEL具有良好的pH敏感性与结肠靶向性。

Abstract:

OBJECTIVE To prepare the pH-sensitive colon-targeting hydrogel of hydrocortisone sodium succinate (HSS-GEL), and to explore its colon targeting. METHODS The preparation process of HSS-GEL was optimized by single factor method. HSS-GEL was prepared with konjac glucomannan (KGM), xanthan gum (XG) and sodium alginate (SA) as hydrogel materials, HSS as a model drug, and glycerol as a delayed release agent. The in vitro release of drug was used as an indicator to investigate the effect of glycerol and its dosage, materials ratio, preparation temperature and drug loading on the release of HSS-GEL. And the release characteristics in different pH media were investigated. The release of HSS-GEL in different tissue homogenates of rats' stomach, small intestine, blind colon and contents was investigated by hatching experiment, and the colon targeting was evaluated. RESULTS The optimal process was as follows:the ratio of KGM-XG-SA was 2.5:4:4, the amount of glycerin was 4% of the prescribed amount, and the preparation temperature was 70℃. The in vitro release results showed that the total release of HSS-GEL in PBS solution at pH 1.2 and pH 6.8 was ≤ 20%, that is, >80% of the drug could enter the medium of pH 7.4. The hatching experiment showed that the concentration of HSS in the blind colon was much larger than that in the stomach and small intestine within 1-10 h, which was greater than the sum of that in the two department at almost every point. CONCLUSION The preparation process of HSS-GEL is simple and stable, and the prepared HSS-GEL has good pH sensitivity and colon targeting.