Departments of Biomedical Engineering and Chemistry, Boston University, Boston, Massachusetts, USA.
J Control Release. 2012 Apr 10;159(1):14-26. doi: 10.1016/j.jconrel.2011.11.031. Epub 2011 Dec 1.
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.
聚合物药物输送库在过去几十年中一直被研究,作为改善肿瘤靶向不足和静脉化疗治疗相关严重全身并发症的手段。这些局部治疗方法有多种形式,旨在以受控的方式将药物直接输送到疾病部位,避免对非目标组织的毒性。许多这些储库是可生物降解的,并设计为在肿瘤部位长时间维持治疗浓度的药物。因此,只需要进行一次植入程序,有时与肿瘤切除手术同时进行,并且在负载的活性药物完全释放后会生物降解。尽管已经研究了局部聚合物储库输送系统,但令人惊讶的是,这些技术中只有一小部分具有潜在的临床前治疗癌症的效果,并且更少的技术已经进展到商业化阶段。本文的目的是回顾过去二十年中研究最多和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、输送)、技术障碍以及该领域的未来展望。