用于肝脏靶向给药的甘草酸稳定槲皮素纳米晶体的制备和体内外评估

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Baode Shen , Yuwen Zhu , Fengxia Wang , Xiang Deng , Pengfei Yue , Hailong Yuan , Chenying Shen
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引用次数: 0

摘要

由于肝细胞中存在甘草酸受体,本研究旨在设计由甘草酸稳定的新型药物纳米晶体(NCs),以实现肝脏靶向给药。槲皮素(QT)在治疗肝脏疾病(包括肝脏脂肪变性、脂肪性肝炎、肝纤维化和肝癌)方面具有良好的药理活性。由于槲皮素的水溶性较差,因此被选为模型药物。通过湿介质研磨技术制备了由 GL 稳定的 QT NCs(QT-NCs/GL),并对其进行了系统评估。制备的 QT-NCs 由 poloxamer 188(QT-NCs/P188)稳定,作为与 QT-NCs/GL 进行体内外性能比较的参照物。通过湿介质研磨技术,成功制备出了粒径在 130 纳米左右的 QT-NCs/GL 和 QT-NCs/P188。在扫描电镜下,QT-NCs/GL 和 QT-NCs/P188 均显示出不规则颗粒和短棒。XRPD 显示 QT-NCs/GL 和 QT-NCs/P188 仍处于结晶状态,结晶度有所降低。与生药 QT 相比,QT-NCs/GL 和 QT-NCs/P188 的溶解度显著提高,药物释放也得到改善。静脉注射 QT-NCs/GL 和 QT-NCs/P188 后,QT 的血浆浓度-时间曲线和药代动力学参数无明显差异。然而,与 QT-NCs/P188 相比,静脉注射 QT-NCs/GL 后 QT 的肝脏分布明显增加,这表明经 GL 稳定的 QT-NCs 可实现 QT 的肝脏靶向给药。由此可以得出结论,GL 用作 QT NCs 的稳定剂在肝脏靶向给药方面具有巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery

The purpose of this study was to design novel drug nanocrystals (NCs) stabilized by glycyrrhizic acid (GL) for achieving liver targeted drug delivery due to the presence of GL receptor in the hepatocytes. Quercetin (QT) exhibits good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It was selected as a model drug owing to its poor water solubility. QT NCs stabilized by GL (QT-NCs/GL) were fabricated by wet media milling technique and systemically evaluated. QT-NCs stabilized by poloxamer 188 (QT-NCs/P188) were prepared as a reference for comparison of in vitro and in vivo performance with QT-NCs/GL. QT-NCs/GL and QT-NCs/P188 with similar particle size around 130 nm were successfully fabricated by wet media milling technique. Both of QT-NCs/GL and QT-NCs/P188 showed irregular particles and short rods under SEM. XRPD revealed that QT-NCs/GL and QT-NCs/P188 remained in crystalline state with reduced crystallinity. QT-NCs/GL and QT-NCs/P188 exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. No significant difference for the plasma concentration–time curves and pharmacokinetic parameters of QT were found following intravenous administration of QT-NCs/GL and QT-NCs/P188. However, a significantly higher liver distribution of QT following intravenous administration of QT-NCs/GL was observed in comparison to QT-NCs/P188, indicating QT-NCs stabilized by GL could achieve liver targeted delivery of QT. It could be concluded that GL used as stabilizer of QT NCs have a great potential for liver targeted drug delivery.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊介绍: International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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