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Supramolecular hydrogel containing multi-generation poly(L-lysine) dendrons for sustained co-delivery of docetaxel and matrix metallopeptidase-9 short hairpin RNA plasmid
Journal of Bioactive and Compatible Polymers ( IF 2.1 ) Pub Date : 2019-12-18 , DOI: 10.1177/0883911519894683
Yumeng Yang 1 , Shixin Liu 1 , Xiang Cai 2 , Dong Ma 1 , Jun Xu 3
Affiliation  

To obtain an efficient drug and gene co-delivery hydrogel, methoxy polyethylene glycol was reacted with the caprolactone units to form the MPEG-PCL block copolymer through the polymerization reaction, which is amphiphilic and can load the hydrophobic drugs. Then, MPEG-PCL conjugated with a multi-generation poly(L-lysine) dendron to form the guest molecule MPEG-PCL-PLLD. After interacted with α-cyclodextrin through host–guest inclusion, the drug and gene dual carrier of supramolecular hydrogel was obtained. The physical properties of the hydrogel, such as the gelation time, the hydrogel strength, or its shear viscosity, could be modulated by the hose molecule of α-cyclodextrin content. MPEG-PCL-PLLD could co-load the drug and gene effectively. After gelation, the loaded drug and gene could be released sustainedly, and the release rate of them was also modulated by the α-cyclodextrin content. The supramolecular hydrogel showed a sustained effect on tumor cells and could induce the cell apoptosis sustainedly. Moreover, the co-delivery strategy was superior to only drug or gene used in tumor cell inhibition. This supramolecular hydrogel as the high-efficiency and sustained co-delivery system showed a promising application in a long-term tumor therapy.

中文翻译:

含有多代聚(L-赖氨酸)树突的超分子水凝胶用于持续共递送多西紫杉醇和基质金属肽酶-9 短发夹 RNA 质粒

为了获得有效的药物和基因共递送水凝胶,甲氧基聚乙二醇与己内酯单元通过聚合反应形成MPEG-PCL嵌段共聚物,该共聚物是两亲性的,可以负载疏水性药物。然后,MPEG-PCL 与多代聚(L-赖氨酸)树突结合形成客体分子 MPEG-PCL-PLLD。通过主客体包合与α-环糊精相互作用后,获得了超分子水凝胶的药物和基因双重载体。水凝胶的物理性质,如凝胶时间、水凝胶强度或其剪切粘度,可以通过 α-环糊精含量的软管分子进行调节。MPEG-PCL-PLLD可以有效地共同加载药物和基因。凝胶化后,负载的药物和基因可以持续释放,它们的释放速率也受α-环糊精含量的调节。超分子水凝胶对肿瘤细胞具有持续作用,并能持续诱导细胞凋亡。此外,共同递送策略优于仅用于肿瘤细胞抑制的药物或基因。这种超分子水凝胶作为高效和持续的共递送系统在长期肿瘤治疗中显示出有希望的应用。
更新日期:2019-12-18
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