Synthetic polymers as drug-delivery vehicles in medicine.
Synthetic polymers as drug-delivery vehicles in medicine.
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合成聚合物作为药物的药物。
DOI：
10.1155/2008/469531
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发表时间：
2008
期刊：
影响因子：
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中科院分区：
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癌症是世界范围内的一个严重的健康问题。虽然癌症的化疗与其他治疗方法相结合已经达到了相当成熟的水平，但这些药物的有效使用仍然受到许多药理缺陷的限制，如较差的水溶性、较短的血清循环寿命以及由于缺乏与癌症组织的亲和力和细胞进入机制不充分而导致的生物利用度低。更关键的是，大多数药物都存在毒副作用和耐药性风险。铂类抗癌药物虽然非常有效，但在这方面尤其臭名昭著。在近年来为克服这些缺陷而开发的无数方法中，聚合物-药物偶联技术作为一种特别先进的治疗方式脱颖而出。该策略涉及药物与水溶性大分子载体的生物可逆结合、结合。按照与普通非聚合物药物截然不同的药代动力学途径，这样得到的结合物将作为前药，安全地将生物活性物质运送到受影响的癌细胞，即其最终的细胞杀伤活性。本论文将向我们介绍这种给药方法的药理学基础，特别适用于金属有机铂类药物体系和有机金属二茂铁药物模型。我们将看到这项技术如何导致在抗增殖活性上明显优于顺铂的结合物，顺铂是临床上使用的抗肿瘤药物。涉及金属和其他药物的聚合物药物结合物无疑已经成熟为制药科学家的实用工具，所有迹象都表明，这种新兴的药物输送方法在抗击癌症和其他人类疾病方面有着辉煌的职业生涯。
Cancerous diseases present a formidable health problem worldwide. While the chemotherapy of cancer, in conjunction with other treatment modalities, has reached a significant level of maturity, efficacious use of such agents is still restricted by numerous pharmacological deficiencies, such as poor water solubility, short serum circulation lifetimes, and low bioavailability resulting from lack of affinity to cancer tissue and inadequate mechanisms of cell entry. More critically still, most drugs suffer from toxic side effects and a risk of drug resistance. The class of platinum anticancer drugs, although outstandingly potent, is particularly notorious in that respect. Among the countless methods developed in recent years in an effort to overcome these deficiencies, the technology of polymer-drug conjugation stands out as a particularly advanced treatment modality. The strategy involves the bioreversible binding, conjugating, of a medicinal agent to a water-soluble macromolecular carrier. Following pharmacokinetic pathways distinctly different from those of the common, nonpolymeric drugs, the conjugate so obtained will act as a prodrug providing safe transport of the bioactive agent to and into the affected, that is, cancerous cell for its ultimate cell-killing activity. The present treatise will acquaint us with the pharmacological fundamentals of this drug delivery approach, applied here specifically to the metalorganic platinum-type drug systems and the organometallic ferrocene drug model. We will see just how this technology leads to conjugates distinctly superior in antiproliferative activity to cisplatin, a clinically used antitumor agent used here as a standard. Polymer-drug conjugation involving metal-based and other medicinal agents has unquestionably matured to a practical tool to the pharmaceutical scientist, and all indications point to an illustrious career for this nascent drug delivery approach in the fight against cancer and other human maladies.