Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (7): 484-501.DOI: 10.5246/jcps.2019.07.047

• Original articles • Previous Articles     Next Articles

Molecular basis for rational construction of RVGP modified liposomal delivery system targeting to brain

Bo Deng1, Wei Cui2, Shuang Ma1, Xiaona Liu1, Zhan Zhang1, Baiyi Yan1, Kun Chen1, 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 Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2019-03-28 Revised:2019-04-11 Online:2019-07-31 Published:2019-05-10
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  • Supported by:

    National Natural Science Foundation of China (Grant No. 81202469).


The rational construction of active targeting liposomes will provide an important structural support for its effective brain targeting. However, there is no clear understanding of the structure-activity relationship of active targeting liposomes. Combining multiscale computational simulation and experimental verification, we established a computational model of RVGP modified PEGylated liposomes (RVGP-PEG-L) and investigated the role of PEG and molecular interaction mechanism of carrier-ligand-receptor. The result indicated that the complex network conformation formed by PEG with 42 monomers (42PEG) above the density of 8% was the molecular basis for PEG-L to achieve long-circulation function. The lowest monomer number of PEG linker to ensure the targeting ability of RVGP was 42. However, the pose of RVGP binding to nAChR changed after it was linked with PEG-L due to the restraint of PEG chain, leading to a decrease of binding free energy. Increasing the monomer number of PEG linker or improving the non-polarity of polymers was a potential strategy to enhance the combination of RVGP-PEG-L with nAChR on the targeting cell. 

Key words: Multiscale dynamic simulation, Liposomes, Molecular interaction mechanism, Rational construction

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