低结晶度聚ε-己内酯电纺膜的制备及其药物控释行为

CONTROLLED RELEASE OF SALICYLIC ACID FROM ELECTROSPUN MATS OF POLY(ε-CAPROLACTONE) WITH LOW CRYSTALLINITY

以芳氧基稀土三(2,6-二叔丁基-4-甲基苯氧基)镧(La(OAr)3)为催化剂,通过加入少量(8.5 mol%)碳酸2,2-二甲基三亚甲基酯(DTC)与ε-己内酯(CL)进行无规共聚合,成功制备了低结晶度的脂肪族内酯-碳酸酯无规共聚酯(PCD)材料,并用1H-NMR、SEC、DSC和WAXS证明了产物的结构和性能.以聚ε-己内酯(PCL)和PCD为基质、以水杨酸为模型药物,通过静电纺丝的方法制备了载药量为8 wt%、直径为1μm的电纺纤维膜,并测试了其体外药物释放行为.结果表明,PCD电纺纤维膜显示了可控的药物缓释行为而PCL电纺纤维则呈现了药物暴释的现象.DSC和WAXS分析表明,这两个体系药物释放行为的差异是由基质结晶度的差别产生的.PCD电纺膜的结晶度(χc=40.3%)远远低于PCL电纺膜(χc=79.3%),且晶区也更加不完善,药物能更多更好地融合在非晶区中,并通过高分子链的热运动缓慢释放.

With the purpose to decrease the crystallinity of poly（ε-caprolactone）（PCL）,a small amount（8.5 mol%） of 2,2-dimethyltrimethylene carbonate（DTC） was added to copolymerize with ε-caprolactone（CL） using lanthanum tris（2,6-di-tert-butyl-4-methylphenolate）（La（OAr）3） as catalyst.The produced polyester P（CL-co-DTC）（PCD） was well-characterized by 1H-NMR,SEC,DSC and WAXS.The results showed random copolymer PCD was synthesized.DSC and WAXS results proved PCD had a much lower crystallinity（χc = 28.1%） compared to that of PCL（χc = 44.7%）.PCD,as well as PCL homopolymer containing 8 wt% salicylic acid as a model drug was electrospun into ultrafine fibers with the diameter around 1 μm and further submitted to in vitro drug release test.The results showed that the PCD electrospun mat exhibited a controlled drug-release behavior while the PCL one displayed a burst-release behavior.The DSC and WAXS results showed PCL electrospun fibers had a much higher crystallinity（χc = 79.3%） than that of PCD electrospun fibers（χc = 40.3%） and this explained the difference of drug-release behaviors of the two electrospun mats.It was the non-crystalline domains involved in PCD that facilitated the compatibility between the polymer matrix and salicylic acid and allowed the drug to be released in a controlled way through the thermal motion of the polymer chain.This study provided a strategy for a better drug inclusion and release behavior by lowering the crystallinity of matrix material.