Ma Ping, Mumper Russell J
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Nanomed Nanotechnol. 2013 Feb 18;4(2):1000164. doi: 10.4172/2157-7439.1000164.
Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.
紫杉醇是有史以来开发出的最有效的化疗药物之一,对多种癌症有效,如肺癌、卵巢癌和乳腺癌。由于其水溶性低,紫杉醇被制成聚氧乙烯蓖麻油(Cremophor EL)和无水乙醇的混合物(50:50,v/v),这种组合被称为泰素(Taxol)。然而,泰素有一些与聚氧乙烯蓖麻油和乙醇相关的严重副作用。因此,迫切需要开发替代的泰素制剂。将紫杉醇封装在可生物降解且无毒的纳米递送系统中,可以保护药物在循环过程中不被降解,进而保护身体免受药物的毒性副作用,从而降低其毒性,延长其循环半衰期,展现出改善的药代动力学特征,并提高患者的依从性。此外,基于纳米颗粒的递送系统可以利用增强的通透性和滞留(EPR)效应进行被动肿瘤靶向,因此,它们是有前景的载体,可提高紫杉醇的治疗指数并降低其副作用。迄今为止,紫杉醇白蛋白结合纳米颗粒(Abraxane®)已被美国食品药品监督管理局(FDA)批准用于治疗转移性乳腺癌和非小细胞肺癌(NSCLC)。此外,还有许多新型紫杉醇纳米颗粒制剂正在进行临床试验。在这篇全面的综述中,将涵盖并讨论几种已开发的紫杉醇纳米递送系统,如聚合物纳米颗粒、脂质体制剂、聚合物缀合物、无机纳米颗粒、碳纳米管、纳米晶体和环糊精纳米颗粒。