Shikanov Ariella, Vaisman Boris, Krasko Michal Y, Nyska Abraham, Domb Abraham J
Department of Medicinal Chemistry and Natural Products, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
J Biomed Mater Res A. 2004 Apr 1;69(1):47-54. doi: 10.1002/jbm.a.20101.
Polyesteranhydrides synthesized by the transesterification of ricinoleic acid and sebacic acid followed by anhydride polymerization were examined as potential controlled delivery carrier for paclitaxel. Solid and liquid polymers were used. Polymers containing 30% ricinoleic acid are solid whereas polymers containing 70% ricinoleic acid are liquid at body temperature and semisolid at room temperature. It was found that upon addition of the liquid polymer to water it solidifies to form a stable semisolid. Paclitaxel, a potent antitumor agent, was incorporated in the polymers (5-20% w/w) and its release in buffer solution was monitored. Paclitaxel was released for over 100 days while the polymer carrier was being degraded. The release rate was affected by the paclitaxel content; the higher the content, the slower was the release. The toxicity of the polymers and formulations with paclitaxel was examined by subcutaneous injection of liquid polymer samples or implantation of solid polymer specimens to mice for different time periods. Histopathological examination of the tissue surrounding the implant showed minor inflammation 1 week after the injection and no inflammation 3 weeks after implantation. Injection of the polymer without paclitaxel showed no adverse effects.
通过蓖麻油酸和癸二酸的酯交换反应接着进行酸酐聚合反应合成的聚（酸酐），被作为紫杉醇潜在的控释载体进行了研究。使用了固态和液态聚合物。含30%蓖麻油酸的聚合物是固态的，而含70%蓖麻油酸的聚合物在体温下是液态的，在室温下是半固态的。发现将液态聚合物加入水中时，它会固化形成稳定的半固态。紫杉醇是一种强效抗肿瘤剂，被掺入聚合物中（5 - 20% w/w），并监测其在缓冲溶液中的释放情况。在聚合物载体降解的同时，紫杉醇释放超过100天。释放速率受紫杉醇含量影响；含量越高，释放越慢。通过将液态聚合物样品皮下注射或向小鼠植入固态聚合物标本不同时间段，来检测聚合物和含紫杉醇制剂的毒性。植入物周围组织的组织病理学检查显示，注射后1周有轻微炎症，植入后3周无炎症。注射不含紫杉醇的聚合物未显示出不良反应。
