Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery

作     者：Shuai Meng Wei Cui Shaohui Lin Guiling Wang Yu Hei Bo Deng Shuang Ma Zhan Zhang Yingchun Liu Ying Xie 孟帅;崔巍;林少辉;王桂玲;黑玉;邓博;马爽;张展;刘迎春;谢英

作者机构：Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery SystemsDepartment of PharmaceuticsSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China School of Chemistry and Chemical EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China Soft Matter Research Center and Department of ChemistryZhejiang UniversityHangzhou 310027ZhejiangChina 

基　　金：The National Natural Science Foundation of China(Grant No.81202469) Founder of new drug research fund(Grant No.20130527) 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2018年第27卷第6期

页      码：415-428页

摘      要：Large Hollow nanoparticulate aggregates（LHNAs） based on albumin nanoparticles is a promising technology for developing dry powder inhaler（DPI） with good aerodynamic properties in order to provide a new drug delivery system（DDS） for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide（BUD） interactions with bovine serum albumin（BSA） at the molecular level. The molecular dynamics（MD） simulation revealed that there were three critical stable binding sites of BUD on BSA（P1, P2, P3） mainly by hydrophobic interaction and hydrogen bond. The energy decomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.

主 题 词：Molecular dynamics Interaction mechanism BSA nanoparticles Budesonide Rational preparation 

学科分类：100702[100702] 1007[医学-药学类] 1006[医学-中西医结合类] 100602[100602] 10[医学] 

核心收录：

D　O　I：10.5246/jcps.2018.06.042

馆 藏 号：203296284...