Jain Jay Prakash, Modi Sweta, Kumar Neeraj
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Mohali 160062, India.
J Biomed Mater Res A. 2008 Mar 1;84(3):740-52. doi: 10.1002/jbm.a.31456.
Low molecular weight hydroxy fatty acid based polyanhydrides were synthesized by one pot method, a variable of typical melt-condensation and characterized by FTIR, NMR, DSC, and GPC. Polymer degrades by both surface and bulk erosion as trailed by weight loss, anhydride loss and surface morphology. Control over drug release was accessed with drugs featuring different aqueous solubility, that is, methotrexate (hydrophobic) and 5-fluorouracil (hydrophilic). Effect of loading, at 5, 10, and 20% w/w of methotrexate on release profiles was also studied and negligible effect was discovered. Biocompatibility of polymers was evaluated in SD rats after SC injection of the polymer. Histopathology revealed initial inflammation of the tissues near the injection site however healed with time. Overall, these polymers were found good to control the release of the entrapped drug and were found biocompatible in preliminary in vivo study. Due to their low melting temperatures they can be injected locally (SC or intratumorally) to from regional in situ depot and have a great potential as a drug carrier for localized delivery of anticancer drugs.
采用一锅法合成了基于低分子量羟基脂肪酸的聚酸酐，这是典型熔融缩聚的一种变体，并通过傅里叶变换红外光谱（FTIR）、核磁共振（NMR）、差示扫描量热法（DSC）和凝胶渗透色谱法（GPC）对其进行了表征。聚合物通过表面侵蚀和本体侵蚀降解，可通过重量损失、酸酐损失和表面形态来追踪。使用具有不同水溶性的药物，即甲氨蝶呤（疏水）和5-氟尿嘧啶（亲水），来控制药物释放。还研究了甲氨蝶呤负载量分别为5%、10%和20%（w/w）时对释放曲线的影响，发现影响可忽略不计。在皮下注射聚合物后，在SD大鼠中评估了聚合物的生物相容性。组织病理学显示注射部位附近的组织最初有炎症，但随时间愈合。总体而言，在初步的体内研究中发现这些聚合物能很好地控制包封药物的释放，并且具有生物相容性。由于它们的低熔点，它们可以局部注射（皮下或瘤内）形成局部原位贮库，作为抗癌药物局部递送的药物载体具有很大潜力。
