Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, QC, Canada H3C 3J7.
J Control Release. 2010 Apr 2;143(1):2-12. doi: 10.1016/j.jconrel.2009.11.012. Epub 2009 Nov 17.
Taxanes are potent antimitotic agents that have demonstrated efficacy in a wide range of malignancies. Due to their poor water-solubility, these cytostatic drugs were first formulated with low molecular weight surfactants, e.g. Cremophor EL (CrEL) and Tween 80 (polysorbate 80), which are known to exhibit serious adverse effects in humans. In recent years, there has been growing interest in the design of more biocompatible formulations for both paclitaxel and docetaxel. Polymer-based drug carriers represent an attractive venue given the diversity in the array of existing polymers. Most notably, biopolyesters are vastly employed in the field of biomedical research given their biocompatibility and biodegradability. Polyester-based micelles and nanoparticles have been applied to the parenteral delivery of taxanes with varying degrees of success. Block copolymer micelles possess a unique core-shell structure generated through the self-assembly of amphiphilic copolymers in aqueous media. Although these systems have shown greatly enhanced tolerability compared to formulations based on low molecular weight surfactants, in some cases their failure to retain their cargo following parenteral administration has hindered their capacity to target taxanes to solid tumours. While polyester-based nanoparticles possess comparatively greater stability and drug targeting capacity, they frequently display a significant burst effect whereby a major portion of the cargo is immediately discarded from the carrier upon injection. This review focuses on the current application of polyester-based micelles and nanoparticles to the tumour targeting of taxanes. The preparation, loading efficiencies, release kinetics, cytotoxicity and in vivo behaviour of these systems is discussed in detail.
紫杉烷类是有效的抗有丝分裂药物，在多种恶性肿瘤中显示出疗效。由于其水溶性差，这些细胞抑制剂药物最初是用低分子量表面活性剂配制的，例如 Cremophor EL（CrEL）和 Tween 80（聚山梨酯 80），已知这些表面活性剂在人类中会产生严重的不良反应。近年来，人们对设计更具生物相容性的紫杉醇和多西紫杉醇制剂越来越感兴趣。鉴于现有聚合物种类繁多，基于聚合物的药物载体具有很大的吸引力。最值得注意的是，由于其生物相容性和可生物降解性，生物聚酯在生物医学研究领域得到了广泛应用。聚酯基胶束和纳米颗粒已被应用于紫杉烷类药物的非肠道给药，取得了不同程度的成功。嵌段共聚物胶束通过两亲性共聚物在水介质中的自组装形成独特的核壳结构。尽管与基于低分子量表面活性剂的制剂相比，这些系统具有更高的耐受性，但在某些情况下，它们在非肠道给药后无法保留其货物，这阻碍了它们将紫杉烷类药物靶向实体瘤的能力。虽然聚酯基纳米颗粒具有相对更高的稳定性和药物靶向能力，但它们经常表现出明显的突释效应，即大部分货物在注射后立即从载体中丢弃。本文综述了聚酯基胶束和纳米颗粒在紫杉烷类药物肿瘤靶向中的最新应用。详细讨论了这些系统的制备、载药效率、释放动力学、细胞毒性和体内行为。
