药物偶联树状聚合物水凝胶通过自切割机制实现药物持续释放。
Drug-Conjugated Dendrimer Hydrogel Enables Sustained Drug Release via a Self-Cleaving Mechanism.
机构信息
Department of Chemical and Life Science Engineering , Virginia Commonwealth University , Richmond , Virginia 23219 , United States.
Department of Biomedical Engineering , Virginia Commonwealth University , Richmond , Virginia 23284 , United States.
出版信息
Mol Pharm. 2019 May 6;16(5):1874-1880. doi: 10.1021/acs.molpharmaceut.8b01207. Epub 2019 Apr 23.
Abstract
In this study, the anticancer drug, camptothecin (CPT), was covalently grafted onto polyamidoamine (PAMAM) dendrimer surface and then reacted with polyethylene glycol diacrylate (PEG-DA) to form dendrimer hydrogel (DH-G3-CPT) with low cross-linking density. In this novel drug delivery system, CPT was cleaved from dendrimer via the ammonolysis of ester bonds and then diffused out of the hydrogel network, thus leading to significantly prolonged drug release. The self-cleaving release kinetics of camptothecin can be further tuned by pH. This DH-G3-CPT drug delivery system has both injectability and sustained drug release. It showed an excellent tumor inhibition effect following intratumoral injection in a head and neck cancer model of mouse.
摘要
在这项研究中，抗癌药物喜树碱（CPT）被共价接枝到聚酰胺-胺（PAMAM）树枝状大分子表面，然后与聚乙二醇二丙烯酸酯（PEG-DA）反应，形成低交联密度的树枝状大分子水凝胶（DH-G3-CPT）。在这个新的药物传递系统中，CPT 通过酯键的氨解从树枝状大分子中裂解出来，然后从水凝胶网络中扩散出来，从而导致药物释放时间显著延长。喜树碱的自裂解释放动力学可以通过 pH 值进一步调节。这种 DH-G3-CPT 药物传递系统具有可注射性和持续的药物释放。在小鼠头颈部癌症模型中，瘤内注射后表现出优异的肿瘤抑制效果。
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