The drug loading behavior of PAMAM dendrimer:Insights from experimental and simulation study  

作　　者：ZHOU LiPing LI JiaWei YU Bing ZHANG Jun HU Hao CONG HaiLin SHEN YouQing 

机构地区：[1]Institute of Biomedical Materials and Engineering,College of Materials Science and Engineering,Qingdao University,Qingdao 266071,China [2]State Key Laboratory of Bio-Fibers and Eco-Textiles,Qingdao University,Qingdao 266071,China [3]Beijing Key Laboratory for Bioengineering and Sensing Technology,School of Chemistry and Biological Engineering,University of Science and Technology Beijing,Beijing 100083,China [4]School of Materials Science and Engineering,China University of Petroleum,Qingdao 266580,China [5]Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education,College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China

出　　处：《Science China(Technological Sciences)》2023年第4期1129-1140,共12页中国科学（技术科学英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.21874078,22074072,and 22274083);the Taishan Young Scholar Program of Shandong Province(Grant No.tsqn20161027);the China Postdoctoral Science Foundation(Grant No.2018M630752);the Postdoctoral Scientific Research Foundation of Qingdao;the Innovation and Development Joint Fund of Natural Science Foundation of Shandong Province(Grant No.ZR2022LZY022);the Science and Technology Planing Project of South District of Qingdao City(Grant No.2022-4-005-YY);the Exploration Project of the State Key Laboratory of Bio Fibers and EcoTextiles of Qingdao University(Grant No.TSKT202101);the High Level Discipline Project of Shandong Province。

摘　　要：Poly(amidoamine)(PAMAM)dendrimers are widely studied as drug vectors due to their particular structure and excellent properties.Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface.In this paper,the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs(doxorubicin(DOX),paclitaxel(TAX),hydroxycamptothecin(HCPT))is studied by molecular dynamics(MD)simulations.Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations,including particle size,drug loading,drug release,and biocompatibility.The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open,and most drug molecules are not completely wrapped.The internal structure of PAMAM dendrimers became looser with more extended nuclei,which increased the non-covalent interactions between PAMAM dendrimers and drug molecules.The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate.This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.

关 键 词：PAMAM DENDRIMER CHEMOTHERAPY molecular dynamics simulation binding energies 

分 类 号：TQ460.4[化学工程—制药化工]