Drug-Conjugated Dendrimer Hydrogel Enables Sustained Drug Release via a Self-Cleaving Mechanism

被引：22
|
作者：
Wang, Juan [1 ]
He, Hongliang [1 ]
Cooper, Remy C. [2 ]
Gui, Qin [1 ]
Yang, Hu [1 ,3 ,4 ]
机构：
[1] Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Richmond, VA 23219 USA
[2] Virginia Commonwealth Univ, Dept Biomed Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA
[3] Virginia Commonwealth Univ, Dept Pharmaceut, Med Coll Virginia Campus, Richmond, VA 23298 USA
[4] Virginia Commonwealth Univ, Massey Canc Ctr, Med Coll Virginia Campus, Richmond, VA 23298 USA
来源：
MOLECULAR PHARMACEUTICS | 2019年 / 16卷 / 05期
基金：
美国国家卫生研究院;
关键词：
dendrimer; hydrogel; self-cleaving; camptothecin; drug delivery; DELIVERY; PLATFORM;
D O I：
10.1021/acs.molpharmaceut.8b01207
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
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-G3CPT 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.
引用
收藏
页码：1874 / 1880
页数：7
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