a Department of Chemistry-Biochemistry and Physics , University of Québec at Trois-Rivières , C. P. 500, Trois-Rivières , Québec G9A 5H7 , Canada.
J Biomol Struct Dyn. 2017 Aug;35(11):2497-2508. doi: 10.1080/07391102.2016.1222971. Epub 2016 Sep 6.
In this review, the binding and loading efficacy (LE) of anticancer drugs doxorubicin (DOX), tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox) with several synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3), and polyamidoamine (PAMAM-G4) dendrimers were compared in aqueous solution at pH 7.4. The results of multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling of conjugated drug-polymer were examined. Structural analysis showed that drug-polymer conjugation occurs mainly via H-bonding and hydrophobic contacts. The order of binding is PAMAM-G4 > mPEG-PAMAM-G3 > PEG-6000 with 4-hydroxttamoxifen forming more stable conjugate than tamoxifen and endoxifen. Doxorubicin shows stronger affinity for PAMAM-G4 than tamoxifen and its metabolites. The drug LE was 30-55%. TEM showed significant changes in the carrier morphology upon drug encapsulation. Modeling also showed that drug is located in the surface and in the internal cavities of PAMAM with DOX forming more stable polymer conjugates.
在这项研究中，比较了几种合成聚合物聚乙二醇（PEG）、甲氧基聚乙二醇聚酰胺胺（mPEG-PAMAM-G3）和聚酰胺胺（PAMAM-G4）树枝状聚合物与阿霉素（DOX）、他莫昔芬（Tam）及其代谢物 4-羟基他莫昔芬（4-Hydroxytam）和依西美坦（Endox）在 pH 7.4 的水溶液中的结合和负载效率（LE）。通过多种光谱方法、透射电子显微镜（TEM）和共轭药物-聚合物的分子建模对结果进行了检查。结构分析表明，药物-聚合物的结合主要通过氢键和疏水相互作用发生。结合顺序为 PAMAM-G4 > mPEG-PAMAM-G3 > PEG-6000，其中 4-羟基他莫昔芬比他莫昔芬和依西美坦形成更稳定的共轭物。阿霉素与 PAMAM-G4 的亲和力强于他莫昔芬及其代谢物。药物 LE 为 30-55%。TEM 显示药物包封后载体形态发生了显著变化。建模还表明，药物位于 PAMAM 的表面和内部腔中，阿霉素形成更稳定的聚合物缀合物。
