School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC.
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan, ROC.
Sci Rep. 2018 May 25;8(1):8092. doi: 10.1038/s41598-018-26432-2.
Complex hydrogels formed with chitosan (CS) and ring-opened polyvinyl pyrrolidone (roPVP) as a swellable mucoadhesive gastroretentive drug dosage form (smGRDDF) were prepared and characterized. CS/roPVP hydrogels were produced by blending CS with roPVP obtained by basic treatment of PVP. Effects of the heating time and NaOH concentration employed for preparing roPVP, and CS molecular weights (Mws), and roPVP/CS ratios on the swelling ability of the resultant hydrogels were characterized. Rheological characteristics were further examined. Results demonstrated that roPVP obtained in a 0.5 M NaOH solution heated to 50 °C for 4 h was suitable for producing complex hydrogels with CS. At a roPVP/CS ratio of 20:1, hydrogels composed of three different Mws of CS possessed optimal swelling and mucoadhesive abilities and rheological properties. In vitro dissolution revealed sustained drug release. A pharmacokinetic study exhibited that the plasma profile of alendronate followed a sustained manner with 3-fold enhancement of the oral bioavailability. In conclusion, the smGRDDF composed of CS/roPVP complex hydrogels was successfully developed and is potentially applicable to improve the clinical efficacy of bisphosphonates.
以壳聚糖（CS）和环开聚乙烯吡咯烷酮（roPVP）为原料制备了可溶胀的黏附性胃滞留药物递送系统（smGRDDF），并对其进行了表征。CS/roPVP 水凝胶是通过将 CS 与通过 PVP 碱性处理得到的 roPVP 混合制备的。考察了制备 roPVP 时加热时间和 NaOH 浓度、CS 分子量（Mw）和 roPVP/CS 比对所得水凝胶溶胀能力的影响。进一步考察了流变特性。结果表明，在 0.5 M NaOH 溶液中于 50°C 加热 4 h 得到的 roPVP 适用于与 CS 制备复合水凝胶。在 roPVP/CS 比为 20:1 时，由三种不同 Mw 的 CS 组成的水凝胶具有最佳的溶胀性、黏附性和流变性能。体外释放结果表明，阿仑膦酸钠的释放具有持续性，口服生物利用度提高了 3 倍。结论：成功开发了由 CS/roPVP 复合水凝胶组成的 smGRDDF，有望提高双膦酸盐类药物的临床疗效。
