• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过实验与分子模拟相结合的方法研究格列吡嗪/环糊精络合作用的分子聚集机制

Investigation of molecular aggregation mechanism of glipizide/cyclodextrin complexation by combined experimental and molecular modeling approaches.

作者信息

Huang Tianhe, Zhao Qianqian, Su Yan, Ouyang Defang

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China.

出版信息

Asian J Pharm Sci. 2019 Nov;14(6):609-620. doi: 10.1016/j.ajps.2018.10.008. Epub 2018 Dec 8.

DOI:10.1016/j.ajps.2018.10.008
PMID:32104487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7032256/
Abstract

Cyclodextrin complexation is a wise strategy to enhance aqueous solubility of water-insoluble drugs. However, the aggregation mechanism of drug-cyclodextrin complexes is still unclear. This research aimed to investigate the molecular aggregation mechanism of glipizide/cyclodextrin complexation by the combination of experimental and modeling methods. Binding free energies between glipizide and cyclodextrins from modeling calculations were higher than those by the phase solubility diagram method. Both experimental and modeling results showed that methylated-β-cyclodextrin exhibited the best solubilizing capability to glipizide. Size-measurement results confirmed the aggregation between glipizide and all four cyclodextrins in high concentrations. Glipizide/γ-cyclodextrin and glipizide/β-cyclodextrin complexes showed stronger aggregation trend than HP-β-cyclodextrin and methylated-β-cyclodextrin. The substituted groups in the rim of HP-β-cyclodextrin and methylated-β-cyclodextrin lead to weak aggregation. This research provided us a clear molecular mechanism of glipizide/cyclodextrin complexation and aggregation. This research will also benefit the formulation development of cyclodextrin solubilization.

摘要

环糊精包合是提高水不溶性药物水溶性的明智策略。然而，药物 - 环糊精复合物的聚集机制仍不清楚。本研究旨在通过实验和建模方法相结合来研究格列吡嗪/环糊精包合的分子聚集机制。建模计算得出的格列吡嗪与环糊精之间的结合自由能高于相溶解度图法所得结果。实验和建模结果均表明，甲基化-β-环糊精对格列吡嗪具有最佳增溶能力。尺寸测量结果证实了高浓度下格列吡嗪与所有四种环糊精之间的聚集。格列吡嗪/γ-环糊精和格列吡嗪/β-环糊精复合物的聚集趋势比羟丙基-β-环糊精和甲基化-β-环糊精更强。羟丙基-β-环糊精和甲基化-β-环糊精边缘的取代基团导致较弱的聚集。本研究为我们提供了格列吡嗪/环糊精包合和聚集的清晰分子机制。该研究也将有助于环糊精增溶制剂的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/03982ed2eb92/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/6356079b9799/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/d262dee6e316/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/d37344f0b879/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/7fc6f2571bb4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/2bad66e85470/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/69e504bd6bf2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/b02c86eb1fbb/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/4fe95e8ffc52/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/03982ed2eb92/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/6356079b9799/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/d262dee6e316/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/d37344f0b879/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/7fc6f2571bb4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/2bad66e85470/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/69e504bd6bf2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/b02c86eb1fbb/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/4fe95e8ffc52/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b10/7032256/03982ed2eb92/gr8.jpg

相似文献

1
Investigation of molecular aggregation mechanism of glipizide/cyclodextrin complexation by combined experimental and molecular modeling approaches.通过实验与分子模拟相结合的方法研究格列吡嗪/环糊精络合作用的分子聚集机制
Asian J Pharm Sci. 2019 Nov;14(6):609-620. doi: 10.1016/j.ajps.2018.10.008. Epub 2018 Dec 8.
2
In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin-epichlorohydrin polymers.格列吡嗪与水溶性β-环糊精-表氯醇聚合物的体外和体内研究。
Drug Dev Ind Pharm. 2011 May;37(5):606-12. doi: 10.3109/03639045.2010.533277.
3
Aggregation of cyclodextrins as an important factor to determine their complexation behavior.环糊精的聚集作为决定其络合行为的一个重要因素。
Chem Biodivers. 2006 Nov;3(11):1266-78. doi: 10.1002/cbdv.200690129.
4
[Solubilization and complexation of the antileukotrienic drug Quinlukast in aqueous solutions of cyclodextrins].[抗白三烯药物喹氯雷司在环糊精水溶液中的增溶与络合作用]
Ceska Slov Farm. 2005 May;54(3):137-40.
5
[The study on the preparation and spectroscopic properties of hydroxypropyl-beta-cyclodextrin/glipizide inclusion complex].羟丙基-β-环糊精/格列吡嗪包合物的制备及光谱性质研究
Guang Pu Xue Yu Guang Pu Fen Xi. 2008 Mar;28(3):711-4.
6
Evaluation of cyclodextrin solubilization of drugs.药物环糊精增溶作用的评估。
Int J Pharm. 2005 Sep 30;302(1-2):18-28. doi: 10.1016/j.ijpharm.2005.05.042.
7
A transdermal delivery system for glipizide.一种用于格列吡嗪的透皮给药系统。
Curr Drug Deliv. 2006 Jul;3(3):333-41. doi: 10.2174/156720106777731037.
8
Encapsulation and Stabilization of α-Lipoic Acid in Cyclodextrin Inclusion Complex Electrospun Nanofibers: Antioxidant and Fast-Dissolving α-Lipoic Acid/Cyclodextrin Nanofibrous Webs.α-硫辛酸包封和稳定在环糊精包合物电纺纳米纤维中：抗氧化和快速溶解的α-硫辛酸/环糊精纳米纤维网。
J Agric Food Chem. 2019 Nov 27;67(47):13093-13107. doi: 10.1021/acs.jafc.9b05580. Epub 2019 Nov 14.
9
Self-assembly of cyclodextrin complexes: aggregation of hydrocortisone/cyclodextrin complexes.环糊精配合物的自组装：氢化可的松/环糊精配合物的聚集。
Int J Pharm. 2011 Apr 4;407(1-2):174-83. doi: 10.1016/j.ijpharm.2011.01.011. Epub 2011 Jan 13.
10
Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies.依托度酸与羟丙基-β-环糊精及辅助剂的包合作用：制剂表征与分子模拟研究
Mol Pharm. 2017 Apr 3;14(4):1231-1242. doi: 10.1021/acs.molpharmaceut.6b01115. Epub 2017 Mar 1.

引用本文的文献

1
Formulation and characterization of eprosartan mesylate and β-cyclodextrin inclusion complex prepared by microwave technology.采用微波技术制备甲磺酸依普罗沙坦和β-环糊精包合物的配方及特性研究。
Drug Deliv. 2022 Dec;29(1):1512-1522. doi: 10.1080/10717544.2022.2072540.
2
The Biological Fate of Pharmaceutical Excipient β-Cyclodextrin: Pharmacokinetics, Tissue Distribution, Excretion, and Metabolism of β-Cyclodextrin in Rats.药用辅料 β-环糊精的生物学命运：β-环糊精在大鼠体内的药代动力学、组织分布、排泄和代谢。
Molecules. 2022 Feb 8;27(3):1138. doi: 10.3390/molecules27031138.
3
Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery.

本文引用的文献

1
Computer-Aided Formulation Design for a Highly Soluble Lutein-Cyclodextrin Multiple-Component Delivery System.基于计算机辅助的叶黄素-环糊精多组分递释系统高溶解性配方设计。
Mol Pharm. 2018 Apr 2;15(4):1664-1673. doi: 10.1021/acs.molpharmaceut.8b00056. Epub 2018 Mar 15.
2
Study on effect of lomefloxacin on human holo-transferrin in the presence of essential and nonessential amino acids: Spectroscopic and molecular modeling approaches.在必需氨基酸和非必需氨基酸存在的情况下洛美沙星对人全转铁蛋白影响的研究：光谱学和分子建模方法
Int J Biol Macromol. 2017 Apr;97:688-699. doi: 10.1016/j.ijbiomac.2017.01.047. Epub 2017 Jan 20.
3
药物研究中分子动力学模拟的机理理解1：药物递送
Front Mol Biosci. 2020 Nov 25;7:604770. doi: 10.3389/fmolb.2020.604770. eCollection 2020.
Interaction of an antiepileptic drug, lamotrigine with human serum albumin (HSA): Application of spectroscopic techniques and molecular modeling methods.
抗癫痫药物拉莫三嗪与人血清白蛋白（HSA）的相互作用：光谱技术和分子建模方法的应用
J Photochem Photobiol B. 2017 Jan;166:187-192. doi: 10.1016/j.jphotobiol.2016.09.046. Epub 2016 Nov 5.
4
Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions.环糊精及其配合物在水溶液中的自组装
J Pharm Sci. 2016 Sep;105(9):2556-2569. doi: 10.1016/j.xphs.2016.01.019. Epub 2016 Mar 12.
5
Relating Protein-Protein Interactions and Aggregation Rates From Low to High Concentrations.关联低浓度至高浓度下的蛋白质-蛋白质相互作用与聚集速率。
J Pharm Sci. 2016 Mar;105(3):1086-96. doi: 10.1016/j.xphs.2016.01.004.
6
Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.蛋白质-配体相互作用的见解：机制、模型与方法
Int J Mol Sci. 2016 Jan 26;17(2):144. doi: 10.3390/ijms17020144.
7
Cyclodextrin-poloxamer aggregates as nanocarriers in eye drop formulations: dexamethasone and amphotericin B.环糊精-泊洛沙姆聚集体作为滴眼剂配方中的纳米载体：地塞米松和两性霉素B。
Drug Dev Ind Pharm. 2016 Sep;42(9):1446-54. doi: 10.3109/03639045.2016.1141932. Epub 2016 Feb 16.
8
MMPBSA.py: An Efficient Program for End-State Free Energy Calculations.MMPBSA.py：用于终态自由能计算的高效程序。
J Chem Theory Comput. 2012 Sep 11;8(9):3314-21. doi: 10.1021/ct300418h. Epub 2012 Aug 16.
9
A New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex.水溶液中γ-环糊精定量测定的新方法：在氢化可的松/γ-环糊精包合物聚集体测定及溶解度中的应用
J Pharm Sci. 2015 Nov;104(11):3925-3933. doi: 10.1002/jps.24608. Epub 2015 Aug 6.
10
Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.难溶性药物格列吡嗪的非泡腾漂浮给药系统的制备及其体外特性研究
Acta Pol Pharm. 2015 Jan-Feb;72(1):193-204.