Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (6): 415-428.DOI: 10.5246/jcps.2018.06.042

• Original articles • Previous Articles     Next Articles

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

Shuai Meng1, Wei Cui2, Shaohui Lin1, Guiling Wang1, Yu Hei1, Bo Deng1, Shuang Ma1, Zhan Zhang1, Yingchun Liu3, Ying Xie1*   

  1. 1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China 
    2. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
    3. Soft Matter Research Center and Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, China
  • Received:2018-04-13 Revised:2018-05-18 Online:2018-06-30 Published:2018-05-23
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  • Supported by:

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


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 energydecomposition 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.

Key words: Molecular dynamics, Interaction mechanism, BSA nanoparticles, Budesonide, Rational preparation

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