Zhang Tao, Tang Yongjia, Zhang Wei, Liu Shan, Zhao Yumei, Wang Wei, Wang Jian, Xu Liang, Liu Keliang
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
J Mater Chem B. 2018 Feb 28;6(8):1216-1225. doi: 10.1039/c7tb03066e. Epub 2018 Feb 7.
Sustained drug release at specific sites is clinically favorable for the treatment of many diseases. The discovery of new polymeric materials suitable for prolonging drug release, improving therapeutic efficiency, and decreasing systemic toxicity is always of great interest in local sustained-release drug delivery systems (LSRDDSs). In this study, a new cross-linked cyanoacrylate (CA)-based LSRDDS is developed, in which the drug depot consists of a formulation of methoxyethyl cyanoacrylate (MOE-CA) with the cross-linking agent CA-PEG-CA. The MOE-CA endowed the CA polymer with good degradability. The drug-release profile could be affected by the structure and composition ratio of the MOE-CA/CA-PEG-CA monomer. The liquid CA monomer could dissolve the drug without using other solvents, and could polymerize into a solid glue just in a few seconds after injection. An optimal formulation loaded with 5-fluorouracil (J-Fu-1.25) showed excellent anticancer activity both in vitro and in vivo, with 50% survival of the mice and no significant systemic toxicity detected during the experiment. The CA depot might affect the blood flow in microvessels of tumors, thus contributing to the synergetic anticancer effect of 5-fluorouracil. We believe that this work provides a practical, biodegradable, and biocompatible LSRDDS for chemotherapeutic drug delivery that can also be applied universally with various drugs for certain therapeutic aims.
在特定部位实现药物持续释放对多种疾病的治疗在临床上是有利的。发现适合延长药物释放、提高治疗效果并降低全身毒性的新型高分子材料一直是局部持续释放给药系统（LSRDDSs）研究的热点。在本研究中，开发了一种基于新型交联氰基丙烯酸酯（CA）的LSRDDS，其中药物储存库由甲氧基乙基氰基丙烯酸酯（MOE-CA）与交联剂CA-PEG-CA的制剂组成。MOE-CA赋予了CA聚合物良好的降解性。药物释放曲线可能会受到MOE-CA/CA-PEG-CA单体的结构和组成比例的影响。液态CA单体无需使用其他溶剂即可溶解药物，并且在注射后几秒钟内即可聚合成固体胶。负载5-氟尿嘧啶的最佳制剂（J-Fu-1.25）在体外和体内均显示出优异的抗癌活性，实验期间小鼠的存活率为50%，且未检测到明显的全身毒性。CA储存库可能会影响肿瘤微血管中的血流，从而有助于5-氟尿嘧啶的协同抗癌作用。我们相信这项工作为化疗药物递送提供了一种实用、可生物降解且生物相容的LSRDDS，该系统也可普遍应用于各种药物以实现特定的治疗目的。
