用于治疗耐药性脑胶质瘤的硼醇改性多西他赛加四氢化萘胶束。

IF 2.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Drug Development and Industrial Pharmacy Pub Date : 2024-02-01 Epub Date: 2024-01-23 DOI:10.1080/03639045.2024.2302886
Yang Liu, Jia-Yu Cai, Yang Liu, Lu Zhang, Rui-Bo Guo, Xue-Tao Li, Ling-Yue Ma, Liang Kong
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引用次数: 0

摘要

目的:胶质瘤是成人中最常见、最致命的原发性恶性肿瘤。由于存在血脑屏障(BBB)、胶质瘤干细胞(GSCs)和多药耐药性(MDR),治疗效果并不理想。多西他赛(DTX)被认为是治疗脑肿瘤的潜在药物,但其生物利用度低和耐药性限制了其疗效。Tetrandrine (TET) 可逆转肿瘤细胞对化疗药物的耐药性。有研究表明,在胶束中修饰的婆罗内酯(BO)可促进 DTX 加 TET 穿过 BBB,使药物更好地作用于肿瘤。因此,我们构建了BO修饰的DTX加TET胶束,以抑制化疗药物的耐药性:意义:为耐药脑胶质瘤提供一种新的治疗方法:本研究采用薄膜分散法制备了BO修饰的DTX加TET胶束,并对其理化性质进行了表征。研究了其靶向能力。结果:BO修饰的DTX加TET胶束具有良好的靶向能力,并通过体内和体外实验研究了其对GSCs的治疗效果:结果:采用薄膜分散法成功构建了BO修饰的DTX加TET胶束,胶束具有良好的稳定性。结果表明,在体外实验中,靶向胶束增加了bEnd.3的吸收,有助于药物通过BBB。我们还发现,靶向胶束能抑制细胞增殖、促进细胞凋亡和抑制耐药蛋白的表达,从而为体外和体内治疗GSCs提供了一种新的方法:BO修饰的DTX加TET胶束可为耐药脑胶质瘤提供一种新的治疗方法。
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Borneol-modified docetaxel plus tetrandrine micelles for treatment of drug-resistant brain glioma.

Objective: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance.

Significance: Provide a new treatment method for drug-resistant brain gliomas.

Methods: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments.

Results: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo.

Conclusions: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

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来源期刊
CiteScore
6.80
自引率
0.00%
发文量
82
审稿时长
4.5 months
期刊介绍: The aim of Drug Development and Industrial Pharmacy is to publish novel, original, peer-reviewed research manuscripts within relevant topics and research methods related to pharmaceutical research and development, and industrial pharmacy. Research papers must be hypothesis driven and emphasize innovative breakthrough topics in pharmaceutics and drug delivery. The journal will also consider timely critical review papers.
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