Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers.
Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers.
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DOI：
10.1016/j.jconrel.2011.11.031
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发表时间：
2012-04-10
期刊：
影响因子：
--
通讯作者：
Grinstaff MW
中科院分区：
文献类型：
--
作者：
Wolinsky JB;Colson YL;Grinstaff MW
过去几十年来，人们对基于聚合物的药物递送储库进行了研究，作为改善与静脉化疗治疗相关的肿瘤靶向缺乏和严重全身性疾病的方法。这些局部疗法以多种形式存在，旨在促进以受控方式将药物直接输送到疾病部位，避免脱靶组织毒性。许多这些储库是可生物降解的，旨在长时间维持肿瘤部位的药物治疗浓度。因此，需要单次植入程序，有时与肿瘤切除手术同时进行，从而在负载的活性剂完全释放后生物降解。尽管已经研究了局部聚合物贮库递送系统，但这些技术中只有一小部分技术已经证明了对癌症应用具有潜在治疗作用的临床前结果，而取得商业化进展的技术则较少。本文的目的是回顾过去二十年中研究最充分、最有效的局部聚合物输送系统，研究在癌症患者中使用药物洗脱聚合物植入物的基本原理，并确定最能从局部治疗中受益的患者群体。最后，讨论了局部治疗的生理障碍（即药物渗透、运输）、技术障碍和该领域的未来前景。
Polymer-based drug delivery depots have been investigated over the last several decades as a means to improve upon the lack of tumor targeting and severe systemic morbidities associated with intravenous chemotherapy treatments. These localized therapies exist in a variety of form factors designed to facilitate the delivery of drug directly to the site of disease in a controlled manner, sparing off-target tissue toxicities. Many of these depots are biodegradable and designed to maintain therapeutic concentrations of drug at the tumor site for a prolonged period of time. Thus a single implantation procedure is required, sometimes coincident with tumor excision surgery, and thereby biodegrading following complete release of the loaded active agent. Even though localized polymer depot delivery systems have been investigated, a surprisingly small subset of these technologies has demonstrated potentially curative preclinical results for cancer applications, and fewer have progressed toward commercialization. The aims of this article are to review the most well-studied and efficacious local polymer delivery systems from the last two decades, to examine the rationale for utilizing drug-eluting polymer implants in cancer patients, and to identify the patient cohorts that could most benefit from localized therapy. Finally, a discussion of the physiological barriers to localized therapy (i.e. drug penetration, transport), technical hurdles, and future outlook of the field is presented.
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