pH-敏感甲硝唑壳聚糖-聚乙烯吡咯烷酮水凝胶的研究

 目的 制备pH-敏感的壳聚糖-聚乙烯吡咯烷酮（PVP）水凝胶，作为甲硝唑治疗胃溃疡控释给药系统的载体。方法 用戊二醛交联适宜比例混合的壳聚糖、PVP混合物，负载甲硝唑或不负载甲硝唑，制备载药水凝胶及空白水凝胶，再冷冻干燥形成半渗透聚合网状物Semi-IPN。用扫描电镜观察性状结构，用测角仪测定其辛烷接触角，用电子天平测其在不同pH介质中的膨胀率，用红外测定了其特征峰，同时考察了载药水凝胶体外释药特性，初步药理实验判断其对实验性胃溃疡的疗效。结果 水凝胶具多孔性，且可很好地负载甲硝唑。辛烷接触角为(143.8±1.02)°，显示本品有较大的亲水性。膨胀率随pH的降低而增大，红外图谱说明水凝胶在酸性介质中膨胀时有-NH₂质子化。甲硝唑在酸性介质中的释放也随pH降低而增大，在pH 1.0介质中，3 h达最大释放量87%。初步药理实验表明，与对照组及甲硝唑片治疗组相比，该甲硝唑水凝胶对胃溃疡具有较优的治疗作用（P分别<0.01及P<0.05）。结论 甲硝唑水凝胶具有pH-敏感膨胀性，可改善甲硝唑对实验性胃溃疡的治疗作用，可作为治疗胃溃疡的新型胃部控释系统研究开发。

pH-sensitive chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for metronidazole delivery

OBJECTIVE To develop a pH-sensitive chitosan-polyvinyl pyrrolidone (PVP) based controlled drug release system for metronidazole delivery METHODS The chitosan-PVP hydrogel was synthesized by cross-linking chitosan and PVP blend (7∶3) with glutaraldehyde. The hydrogel was then freeze-dried to form a semi-interpenetrating polymer network (semi-IPN). The characters of the hydrogel, including morphology, octane contact angle and pH-dependent swelling properties were studied using scanning electronic microscopy, goniometer and electronic balance respectively. The semi-IPN formation was confirmed by Fourier transform infrared spectroscopic (FTIR) analysis. The release of metronidazole was also detected in-vitro Preliminary pharmacological test was employed to evaluate the effect of metronidazole hydrogel on gastric ulcer RESULTS Porous freeze-dried hydrogel ［pore diameter (35.77±6.14) μm］ exhibited excellent pH-dependent swelling properties. A large octane contact angle (143.8±1.02)° of the hydrogel was indicative of its hydrophilic nature. Increased swelling of hydrogel under acidic condition was due to the protonation of the amine groups on chitosan, which was confirmed by FTIR analysis. The hydrogel released around 87% of metronidazole in 3 h at pH 1.0 in-vitro and thus had a promising gastric-targeting release property. The hydrogel entrapped with metronidazole had better effect on gastric ulcer compared with the control group (P<0.01) and metronidazole tablet group (P<0.05) CONCLUSION The pH-sensitive swelling hydrogel containing metronidazole was a good candidate for further study as a new anti-gastric ulcer preparation.