伊曲康唑脂质体的制备及评价及其对 Hedgehog 通路的抑制作用。

Formulation and evaluation of itraconazole liposomes for Hedgehog pathway inhibition.

机构信息

Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.

出版信息

J Liposome Res. 2020 Sep;30(3):305-311. doi: 10.1080/08982104.2019.1668011. Epub 2019 Oct 2.

Abstract

Itraconazole (ITZ) is an FDA-approved antifungal agent that has recently been explored for novel biological properties. In particular, ITZ was identified as a potent inhibitor of the hedgehog (Hh) pathway, a cell signalling pathway that has been linked to a variety of cancers and accounts for ∼25% of paediatric medulloblastoma (MB) cases. To date, there is not a targeted therapeutic option for paediatric MB, resulting in long-term side effects such as hormone deficiency, organ damage and secondary cancers. A primary obstacle for developing targeted therapy for brain ailments is the presence of the blood-brain barrier (BBB), which protects the brain from potentially harmful substances. Due to its size and hydrophobicity, ITZ does not penetrate the BBB. Alternatively, liposomes are being increasingly used within the clinic to increase drug bioavailability, target specificity and BBB permeability. With this in mind, we have successfully developed ITZ-containing liposomes with an optimal size for BBB penetration (<100 nm) and encapsulation efficiency (∼95%) by utilizing a continuous manufacturing approach-turbulent coaxial jet in co-flow. Our preliminary data demonstrate that these liposomes inhibit the Hh pathway, albeit at a reduced level in comparison to free ITZ. (196/250 words).

摘要

伊曲康唑(ITZ)是一种获得美国食品药品监督管理局批准的抗真菌药物,最近其新的生物学特性被广泛研究。特别是,ITZ 被鉴定为 Hedgehog(Hh)信号通路的有效抑制剂,Hh 信号通路与多种癌症有关,约占儿童髓母细胞瘤(MB)病例的 25%。迄今为止,对于儿童 MB 还没有靶向治疗选择,导致长期副作用,如激素缺乏、器官损伤和继发性癌症。针对脑部疾病开发靶向治疗的一个主要障碍是血脑屏障(BBB)的存在,它保护大脑免受潜在有害物质的侵害。由于其大小和疏水性,ITZ 无法穿透 BBB。相反,脂质体在临床上越来越多地被用于提高药物的生物利用度、靶向特异性和 BBB 通透性。考虑到这一点,我们通过利用连续制造方法-同轴射流中的湍流共流,成功地开发了具有最佳 BBB 穿透性(<100nm)和包封效率(~95%)的含有 ITZ 的脂质体。我们的初步数据表明,这些脂质体抑制了 Hh 通路,尽管与游离 ITZ 相比,抑制作用有所降低。(196/250 个词)。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索