Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi-180001, India.
Curr Drug Deliv. 2014;11(6):666-86. doi: 10.2174/1567201811666140609154949.
Paclitaxel (PTX), a taxane plant product, is one of the most effective broad-spectrum anti-cancer agents and approved for the treatment of a variety of cancers including ovarian, breast, lung, head and neck as well as Kaposi's sarcoma. Poor aqueous solubility and serious side effects associated with commercial preparation of PTX (Taxol®) triggered the development of alternative PTX formulations. Over past three decades, plethora of research work has been published towards the development of cremophor free and efficient formulations. Various nanocarrier systems including nanoparticles, liposomes, micelles, bioconjugates and dendrimers have been employed in order to improve PTX solubility and eliminate undesired side effects. These nanocarriers offer the advantage of high degree of encapsulation and cellular uptake, escape from elimination by P-glycoprotein (P-gp) mediated efflux, and can be explored for targeted drug delivery. The potential of these nanocarriers is reflected by the fact that various nanocarriers of PTX are in different stages of clinical trials and a few have already been commercialized including Abraxane®, Lipusu and Genexol PM®. This review focuses on the various challenges associated with PTX formulation development, limitations of existing formulations and novel approaches for the development of alternative formulations for PTX and also highlights the development of novel formulations in clinical settings.
紫杉醇（PTX）是一种紫杉烷植物产物，是最有效的广谱抗癌药物之一，已被批准用于治疗多种癌症，包括卵巢癌、乳腺癌、肺癌、头颈部癌和卡波济肉瘤。紫杉醇（Taxol®）商业制剂的水溶性差和严重的副作用促使人们开发替代的 PTX 制剂。在过去的三十年中，已经发表了大量的研究工作，致力于开发无 Cremophor 且高效的制剂。为了提高 PTX 的溶解度并消除不良副作用，已经采用了各种纳米载体系统，包括纳米粒、脂质体、胶束、生物缀合物和树枝状大分子。这些纳米载体具有高封装度和细胞摄取的优势，可以逃避 P-糖蛋白（P-gp）介导的外排作用，并可用于靶向药物递送。这些纳米载体的潜力反映在以下事实中：PTX 的各种纳米载体处于不同的临床试验阶段，其中一些已经商业化，包括 Abraxane®、Lipusu 和 Genexol PM®。本文综述了与 PTX 制剂开发相关的各种挑战、现有制剂的局限性以及开发替代 PTX 制剂的新方法，并强调了临床新制剂的开发。
