Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study

doi:10.1007/s40436-015-0120-7

Advances in Manufacturing ›› 2015, Vol. 3 ›› Issue (3): 221-231.doi: 10.1007/s40436-015-0120-7

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Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study

Fa-Da Zhang^1,2,3, Yi Liu^1,2, Jing-Cheng Xu², Sheng-Juan Li², Xiu-Nan Wang^2,3, Yue Sun², Xin-Luo Zhao¹

1 Department of Physics and Materials Genome Institute, Shanghai University, Shanghai 200444, P. R. China;
2 School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China;
3 School of Energy & Power Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China

Received:2015-05-15 Revised:2015-08-16 Online:2015-09-25 Published:2015-09-22
Contact: Yi Liu, Jing-Cheng Xu E-mail:YiLiu@shu.edu.cn;jchxu@usst.edu.cn
Supported by:
The authors are grateful for financial supports from “Shanghai Pujiang Talent” program (Grant No. 12PJ1406500), “Shanghai High-tech Area of Innovative Science and Technology (Grant No. 14521100602)”, STCSM; “Key Program of Innovative Scientific Research” (Grant No. 14ZZ130) and “Key Laboratory of Advanced Metal-based Electrical Power Materials”, the Education Commission of Shanghai Municipality; State Key Laboratory of Heavy Oil Processing, China University of Petroleum (Grant No. SKLOP201402001); National Natural Science Foundation of China (Grant Nos. 51202137, 61240054, and 11274222).

Abstract

Abstract: All atomistic molecular dynamics simulations were performed on poly (amidoamine) (PAMAM) dendrimers that compound non-covalently with anticancer drug molecules including DOX, MTX, CE6, and SN38. The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug, PAMAM, and PEG chains. We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding. It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement. Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion. This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems.

Key words: Dendrimer, PAMAM, PEGylation, Anticancer drug, Drug delivery systems, Molecular dynamics

Fa-Da Zhang, Yi Liu, Jing-Cheng Xu, Sheng-Juan Li, Xiu-Nan Wang, Yue Sun, Xin-Luo Zhao. Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study[J]. Advances in Manufacturing, 2015, 3(3): 221-231.

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Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study

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