Designing Paclitaxel drug delivery systems aimed at improved patient outcomes: current status and challenges.
Designing Paclitaxel drug delivery systems aimed at improved patient outcomes: current status and challenges.
复制标题
DOI：
10.5402/2012/623139
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Das NG
中科院分区：
文献类型：
--
作者：
Surapaneni MS;Das SK;Das NG
紫杉醇是最广泛使用和有效的天然来源的抗肿瘤剂之一。它具有广谱抗肿瘤活性，特别是对卵巢癌、乳腺癌、非小细胞肺癌、头颈部肿瘤、卡波西肉瘤和泌尿系统恶性肿瘤。它是一种高度亲脂性化合物，log P值为3.96，水溶性极差，小于0.01 mg/mL。此外，该化合物缺乏可电离的官能团，这可能导致其溶解度随着pH值的改变而增加。因此，紫杉醇的递送与实质性挑战相关。在引入Abraxane之前，唯一的商业制剂是紫杉醇在Cremophor中的溶液，这会引起严重的副作用。然而，近年来，已经报道了许多使用共溶剂和包合络合物来溶解紫杉醇的方法。此外，已经报道了使用纳米颗粒、纳米混悬剂、脂质体、乳剂、胶束、植入物、糊剂和凝胶被动靶向肿瘤的创新方法。本文讨论了改善治疗效果的所有方法。
Paclitaxel is one of the most widely used and effective antineoplastic agents derived from natural sources. It has a wide spectrum of antitumor activity, particularly against ovarian cancer, breast cancer, nonsmall cell lung cancer, head and neck tumors, Kaposi's sarcoma, and urologic malignancies. It is a highly lipophilic compound with a log P value of 3.96 and very poor aqueous solubility of less than 0.01 mg/mL. In addition, the compound lacks functional groups that are ionizable which could potentially lead to an increase in its solubility with the alteration in pH. Therefore, the delivery of paclitaxel is associated with substantial challenges. Until the introduction of Abraxane, only commercial formulation was solution of paclitaxel in cremophor, which caused severe side effects. However, in recent years, a number of approaches have been reported to solubilize paclitaxel using cosolvents and inclusion complexes. In addition, innovative approaches have been reported for passive targeting of tumors using nanoparticles, nanosuspensions, liposomes, emulsions, micelles, implants, pastes and gels. All approaches for delivery of improved therapeutic outcome have been discussed in this paper.