Qiu L Y, Zhu K J
College of Pharmaceutical Science, Zhejiang University, 310006, Hangzhou, People's Republic of China.
Int J Pharm. 2001 May 21;219(1-2):151-60. doi: 10.1016/s0378-5173(01)00644-5.
A cylindrical dosage form comprising a laminated composite polymer core and a hydrophobic polycarbonate coating was proposed for programmable drug delivery. In the core, poly[(ethyl glycinate) (benzyl amino acethydroxamate) phosphazene] was synthesized as drug-loaded layers for its strong pH-sensitive degradation (eroded after 1.5 days at pH 7.4 and more than 20 days at pH 5.0 and 6.0). Poly(sebacic anhydride)-b-polyethylene glycol or poly(sebacic anhydride-co-trimellitylimidoglycine)-b-poly(ethylene glycol) was selected as isolating layers for their good processing properties at room temperature and suitable erosion duration. The in vitro drug release studies of these devices were conducted under physiological conditions (pH 7.4). The results revealed that the model drugs (brilliant blue, FITC-dextran, myoglobin) could be released in typical pulsatile manner. Moreover, the duration time of drug release (24-40 h) and the lag time (18-118 h) could be separately regulated by the mass of polyphosphazene and the type or mass of polyanhydride. In this experiment, the cooperative effect of polyanhydrides and pH-sensitive degradable polyphosphazene was specially demonstrated, which offers a new idea to develop a programmable drug delivery system for single dose vaccine and other related applications.
提出了一种包含层压复合聚合物核心和疏水性聚碳酸酯涂层的圆柱形剂型用于可编程药物递送。在核心中，合成了聚[(乙基甘氨酸)(苄基氨基乙酰氧肟酸)磷腈]作为载药层，因为其具有很强的pH敏感性降解特性（在pH 7.4时1.5天后被侵蚀，在pH 5.0和6.0时超过20天后被侵蚀）。选择聚(癸二酸酐)-b-聚乙二醇或聚(癸二酸酐-共-偏苯三酸酰亚胺甘氨酸)-b-聚(乙二醇)作为隔离层，因为它们在室温下具有良好的加工性能和合适的侵蚀持续时间。在生理条件（pH 7.4）下对这些装置进行了体外药物释放研究。结果表明，模型药物（亮蓝、异硫氰酸荧光素标记的葡聚糖、肌红蛋白）可以以典型的脉冲方式释放。此外，药物释放的持续时间（24 - 40小时）和滞后时间（18 - 118小时）可以分别通过聚磷腈的质量以及聚酸酐的类型或质量来调节。在本实验中，特别证明了聚酸酐和pH敏感可降解聚磷腈的协同作用，这为开发用于单剂量疫苗和其他相关应用的可编程药物递送系统提供了新思路。
