Multifunctional Docetaxel Cholesterol-Polyethylene Glycol Co-Modified Poly (N-Butyl) Cyanoacrylate Nanoparticles for Brain Tumor Therapy

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2025-02-27 DOI:10.1002/ddr.70069

Xiao Hu, Feifei Yang, Yonghong Liao, Lin Li, Lan Zhang

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Abstract

Owing to the presence of the blood-brain barrier and the lack of significant specificity towards tumor cells after entry into the brain, the unsuccessful delivery of anticancer drugs to the treatment of brain tumors. The hypothesis that cholesterol-PEG co-modified poly (N-butyl) cyanoacrylate nanoparticles (CLS-PEG NPs) are an effective carrier for the treatment of brain tumors was verified, and the mechanism of its treatment for brain tumors was preliminarily explored. In this study, we used multifunctional poly (N-butyl) cyanoacrylate nanoparticles modified with cholesterol and polyethylene glycol (PEG) as a drug delivery system to encapsulate the anticancer drug docetaxel (DTX). Cell anti-proliferation tests showed that CLS-PEG NPs increased the inhibitory effect of DTX. A pharmacokinetic study indicated that CLS-PEG NPs achieved sustained release for 8 h. These experimental results demonstrated that CLS-PEG NPs amplified the concentration of the drug transported to the brain and sustained drug release in the brain. In addition, CLS-PEG NPs led to better pharmacological efficacy in an orthotopic brain glioma rat model. The survival rate of rats in the CLS-PEG NPs group was significantly prolonged to 28 d. We also found that CLS-PEG NPs inhibited M2 microglial polarization. These results indicate that CLS-PEG NPs are a prospective drug delivery system for targeting brain tumors.

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多功能多西他赛胆固醇-聚乙二醇共修饰聚（n -丁基）氰丙烯酸酯纳米颗粒用于脑肿瘤治疗

由于血脑屏障的存在以及进入大脑后对肿瘤细胞缺乏明显的特异性，抗癌药物的输送治疗脑肿瘤失败。验证了胆固醇-聚乙二醇共修饰聚（n -丁基）氰基丙烯酸酯纳米颗粒（CLS-PEG NPs）是治疗脑肿瘤的有效载体的假设，并初步探讨了其治疗脑肿瘤的机制。在这项研究中，我们使用胆固醇和聚乙二醇（PEG）修饰的多功能聚（n -丁基）氰基丙烯酸酯纳米颗粒作为药物递送系统来封装抗癌药物多西紫杉醇（DTX）。细胞抗增殖实验表明，CLS-PEG NPs增强了DTX的抑制作用。药代动力学研究表明，CLS-PEG NPs达到8小时的缓释。这些实验结果表明，CLS-PEG NPs增加了药物转运到大脑的浓度，并持续了药物在大脑中的释放。此外，CLS-PEG NPs在正位脑胶质瘤大鼠模型中具有较好的药理作用。CLS-PEG NPs组大鼠存活率显著延长至28 d。我们还发现CLS-PEG NPs抑制M2小胶质细胞极化。这些结果表明，CLS-PEG NPs是一种有前景的靶向脑肿瘤的药物传递系统。

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来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.