Delivery of anticancer drugs.
Delivery of anticancer drugs.
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抗癌药物的输送。
DOI：
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发表时间：
1989
影响因子：
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通讯作者：
C. Cheng
中科院分区：
文献类型：
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作者：
R. K. Zee;C. Cheng
化疗是治疗局部和转移性癌症的主要治疗方法。由于抗癌药物对癌细胞既无特异性也无靶向，因此改善抗癌药物向人体肿瘤组织的递送似乎是一个合理且可实现的挑战。科学家们正在努力通过以下方式增加肿瘤吸收药物的可用性：1）延迟释放制剂以实现持久作用; 2）使用脂质体包埋药物以延长效果或降低毒性; 3）在肿瘤部位施用惰性无毒前药以进行特异性激活; 4）递送抗体介导的药物;或5）结合位点特异性载体以将药物导向肿瘤靶点。后者在很大程度上取决于药代动力学研究。在提高药物疗效和降低毒性方面取得了一些成功。药代动力学和药效学的考虑是两个领域，已集中对抗癌药物的定量药理学研究在这篇手稿。本文综述了生物分布和消除，提供信息的身体清除和主要代谢的揭示网站;通过各种途径的抗癌药物管理的最佳利用;局部肿瘤动脉内灌注，鞘内，腹腔内和胸膜内注射区域腔管理。列出了治疗性抗癌药物的常规给药途径、剂量、药代动力学数据和消除途径。一般的抗癌药物在实现治疗的改善交付的方法进行了概述和相关。耐药性的机制，和具体的变化，影响现有的化疗药物的交付，以及药物，以恢复耐药肿瘤细胞的药物的敏感性，进行了讨论。本专著从两个方面介绍了抗癌药物的发展和进展：理论方面，包括药代动力学和药效学方面的考虑，治疗意义和耐药机制;实践方面，包括物理，化学，生物化学和生理学方面的考虑。其中，用于将抗癌剂递送至靶位点的物理方法（通过微粒药物载体：纳米颗粒、脂质体、微球和活性炭以及磁性微胶囊）在延长抗癌作用和降低毒性方面显示出可识别的改进。用于区域化疗的植入式泵和储药器提供了输送速率的外部控制。一般来说，植入系统在治疗肝癌和脑癌方面比传统治疗方法效果更好。用于改善药物递送的化学方法使用前药、生物可降解聚合物和大分子基质技术。（400字处截断摘要）
Chemotherapy is a major therapeutic approach for the treatment of both localized and metastasized cancers. Since anticancer drugs are neither specific nor targeted to the cancer cells, improved delivery of anticancer drugs to tumor tissues in humans appears to be a reasonable and achievable challenge. Scientists are working to increase the availability of drug for tumor uptake by 1) delaying the release preparations for long-lasting actions; 2) using liposome-entrapped drugs for prolonged effect or reduced toxicity; 3) administrating inert, non-toxic prodrugs for specific activation at the tumor site; 4) delivering the antibody-mediated drugs; or 5) conjugating site-specific carriers to direct the drug to the tumor target. The latter depends heavily on pharmacokinetic investigations. Some success has been achieved in enhancing the efficacy and reducing the toxicity of drugs. Pharmacokinetic and pharmacodynamic considerations are two areas which have been focused toward the quantitative pharmacological studies of anticancer drugs in this manuscript. This review covers biodistribution and elimination, furnishing information on body clearance and unveiling sites of major metabolism; administration of anticancer drugs via various routes for optimal utilization; intra-arterial infusion for localized tumors, intrathecal, intraperitoneal and intrapleural injection for regional cavity administration. Conventional delivery routes, doses, pharmacokinetics data and elimination routes of therapeutic anticancer drugs are tabled. General approaches for delivery of anticancer drugs in achieving therapeutic improvements are outlined and correlated. Mechanism of drug resistance, and specific changes affecting the delivery of available chemotherapeutic agents, as well as the drugs to restore the sensitivities to agents of resistant tumor cells, are discussed. This monograph covers the developments and progress in the delivery of anticancer drugs in two approaches: the theoretical approach, including pharmacokinetic and pharmacodynamic considerations, therapeutic implications and mechanism of drug resistance, and the practical approach, including the physical, chemical, biochemical and physiological considerations. Among these, the physical approach for the delivery of anticancer agents to target sites (via microparticulate drug carriers: nanoparticles, liposomes, microspheres and activated carbon as well as the magnetic microcapsules) has shown recognizable improvements in prolonging anticancer effects and reducing toxicities. Implantable pumps and reservoirs for regional chemotherapy provide external control of delivery rate. The implanted systems, in general, yield better results than the traditional treatments in the treatment of liver and brain cancer. Chemical approaches for the improvement of drug delivery use prodrugs, biodegradable polymers and macromolecular matrix techniques.(ABSTRACT TRUNCATED AT 400 WORDS)