Wersig T, Hacker M C, Kressler J, Mäder K
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06099 Halle (Saale), Germany.
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, D-04317 Leipzig, Germany.
Int J Pharm. 2017 Oct 5;531(1):225-234. doi: 10.1016/j.ijpharm.2017.08.093. Epub 2017 Aug 23.
The linear biodegradable polyester poly(glycerol adipate) (PGA) was synthesized via enzymatic polycondensation using lipase B from Candida antarctica (CAL-B). Every monomer unit of PGA possesses a pendant hydroxyl group which is responsible for the hydrophilic character and moisture swelling. These OH groups were esterified to different degrees with the anti-inflammatory drug indomethacin in order to create a prodrug with a pH-sensitive linker for modified drug release. The structure of the conjugates was determined via ATR FT-IR spectroscopy, NMR spectroscopy, GPC and UV/VIS spectroscopy. The physical properties of polymers with different drug load were investigated using DSC, contact angle measurements and oscillatory rheology. Drug release was monitored over one month in vitro. A very slow, but continuous release was observed in PBS. Slightly acidic conditions and lipase activity are accelerating the indomethacin release. Therefore, poly(glycerol adipate) - indomethacin conjugates are promising prodrugs for the local sustained release of indomethacin.
通过使用来自南极假丝酵母的脂肪酶B（CAL-B）进行酶促缩聚反应，合成了线性可生物降解聚酯聚（己二酸甘油酯）（PGA）。PGA的每个单体单元都有一个侧链羟基，该羟基赋予了其亲水性和吸湿膨胀性。这些羟基与抗炎药物吲哚美辛进行了不同程度的酯化反应，以制备一种具有pH敏感连接子的前药，用于药物的改性释放。通过ATR傅里叶变换红外光谱、核磁共振光谱、凝胶渗透色谱和紫外/可见光谱确定了缀合物的结构。使用差示扫描量热法、接触角测量和振荡流变学研究了不同载药量聚合物的物理性质。在体外监测了药物释放一个月。在磷酸盐缓冲盐溶液（PBS）中观察到非常缓慢但持续的释放。略酸性条件和脂肪酶活性会加速吲哚美辛的释放。因此，聚（己二酸甘油酯）-吲哚美辛缀合物是用于吲哚美辛局部持续释放的有前景的前药。
