Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy.
Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy.
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DOI：
10.1016/j.jconrel.2017.09.026
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发表时间：
2017-12-10
期刊：
影响因子：
--
通讯作者：
Cui H
中科院分区：
文献类型：
--
作者：
Wang F;Porter M;Konstantopoulos A;Zhang P;Cui H
紫杉醇（PTX）是有史以来用于癌症化疗的最成功的药物之一，对多种癌症类型有效。用Cremophor EL和乙醇（Taxol®）配制PTX实现了其临床潜力，但由于副作用如周围神经病变、低血压和超敏反应，该制剂福尔斯不到预期。Abraxane®，白蛋白结合的PTX，代表减轻Cremophor EL相关副作用的Taxol®的上级替代品。虽然Abraxane®现在被认为是化疗的金标准，但其21%的反应率仍有很大的改进空间。对更安全、更有效的癌症治疗的追求导致了大量创新PTX制剂的开发，其中许多目前正在进行临床试验。在此背景下，我们回顾了最近的发展PTX给药系统和分析的设计原则支撑每一个交付策略。我们选择了几个有代表性的例子来强调聚合物系统，脂质制剂以及前药策略的机遇和挑战。目前正在进行临床前开发的紫杉醇输送的代表性平台技术。
Paclitaxel (PTX) is one of the most successful drugs ever used in cancer chemotherapy, acting against a variety of cancer types. Formulating PTX with Cremophor EL and ethanol (Taxol®) realized its clinical potential, but the formulation falls short of expectations due to side effects such as peripheral neuropathy, hypotension, and hypersensitivity. Abraxane®, the albumin bound PTX, represents a superior replacement of Taxol® that mitigates the side effects associated with Cremophor EL. While Abraxane® is now considered a gold standard in chemotherapy, its 21% response rate leaves much room for further improvement. The quest for safer and more effective cancer treatments has led to the development of a plethora of innovative PTX formulations, many of which are currently undergoing clinical trials. In this context, we review recent development of PTX drug delivery systems and analyze the design principles underpinning each delivery strategy. We chose several representative examples to highlight the opportunities and challenges of polymeric systems, lipid-based formulations, as well as prodrug strategies. Representative platform technologies for paclitaxel delivery currently under preclinical development.
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