Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
Department of pharmaceutics, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
J Control Release. 2019 Oct;311-312:125-137. doi: 10.1016/j.jconrel.2019.08.034. Epub 2019 Aug 30.
Ovarian carcinoma (OC) is one of the leading causes of death among gynecologic malignancies all over the world. It is characterized by high mortality rate because of the lack of early diagnosis. The first-line chemotherapeutic regimen for late stage epithelial ovarian cancer is paclitaxel in combination to carboplatin. However, in most of cases, relapse occurs within six months despite the initial success of this chemotherapeutic combination. A lot of challenges have been encountered with the conventional delivery of paclitaxel in addition to the occurrence of severe off-target toxicity. One major problem is poor paclitaxel solubility which was improved by addition of Cremophor EL that unfortunately resulted in hypersensitivity side effects. Another obstacle is the multi drug resistance which is the main cause of OC recurrence. Accordingly, incorporation of paclitaxel, solely or in combination to other drugs, in nanocarrier systems has grabbed attention of many researchers to circumvent all these hurdles. The current review is the first article that provides a comprehensive overview on multi-faceted implementations of paclitaxel loaded nanoplatforms to solve delivery obstacles of paclitaxel in management of ovarian carcinoma. Moreover, challenges in physicochemical properties, biological activity and targeted delivery of PTX were depicted with corresponding solutions using nanotechnology. Different categories of nanocarriers employed were collected included lipid, protein, polymeric, solid nanoemulsion and hybrid systems. Future perspectives including imperative research considerations in ovarian cancer therapy were proposed as well.
卵巢癌 (OC) 是全世界妇科恶性肿瘤死亡的主要原因之一。由于缺乏早期诊断,其死亡率很高。晚期上皮性卵巢癌的一线化疗方案是紫杉醇联合卡铂。然而,尽管这种化疗联合取得了初步成功,但大多数情况下仍会在六个月内复发。除了严重的脱靶毒性外,紫杉醇的常规给药还存在许多挑战。一个主要问题是紫杉醇的溶解度差,通过添加 Cremophor EL 得到了改善,但不幸的是这导致了过敏副作用。另一个障碍是多药耐药性,这是 OC 复发的主要原因。因此,将紫杉醇单独或与其他药物一起纳入纳米载体系统已引起许多研究人员的关注,以克服所有这些障碍。这篇综述是第一篇全面概述载紫杉醇纳米平台的多方面实施,以解决卵巢癌管理中紫杉醇的递药障碍的文章。此外,还通过纳米技术描绘了 PTX 在理化性质、生物活性和靶向递送方面的挑战及相应的解决方案。收集了不同类别的纳米载体,包括脂质体、蛋白质、聚合物、固态纳米乳剂和混合系统。还提出了未来的展望,包括卵巢癌治疗中必要的研究考虑因素。