用于阿霉素递送的组蛋白去乙酰化酶抑制剂共轭聚合物前药胶束
HDAC Inhibitor Conjugated Polymeric Prodrug Micelles for Doxorubicin Delivery.
作者信息
Senevirathne Suchithra A, Washington Katherine E, Miller Jason B, Biewer Michael C, Oupicky David, Siegwart Daniel J, Stefan Mihaela C
机构信息
Department of Chemistry, University of Texas at Dallas, Richardson, TX, USA.
Department of Biochemistry, University of Texas Southwestern Medical Center, Simmons Comprehensive Cancer Center, Dallas, TX, USA.
出版信息
J Mater Chem B. 2017 Mar 21;5(11):2106-2114. doi: 10.1039/C6TB03038F. Epub 2017 Feb 20.
Abstract
Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) were synthesized by the ring-opening polymerization of γ-4-phenylbutyrate-ε-caprolactone (PBACL), γ-valproate-ε-caprolactone (VPACL), and ε-caprolactone (CL) from a poly(ethylene glycol) macroinitiator (PEG). These amphiphilic diblock copolymers self-assembled into stable pro-drug micelles and demonstrated excellent biocompatibility. High loading of doxorubicin (DOX) up to 5.1 wt% was achieved. Optimized micelles enabled sustained drug release in a concentration-dependent manner over time to expand the therapeutic window of cytotoxic small molecule drugs.
摘要
通过聚乙二醇（PEG）大分子引发剂引发γ-4-苯基丁酸-ε-己内酯（PBACL）、γ-丙戊酸-ε-己内酯（VPACL）和ε-己内酯（CL）的开环聚合反应，合成了带有组蛋白去乙酰化酶抑制剂（HDACi）（4-苯基丁酸和丙戊酸）的两亲性二嵌段共聚物。这些两亲性二嵌段共聚物自组装成稳定的前药胶束，并表现出优异的生物相容性。实现了高达5.1 wt%的阿霉素（DOX）高负载量。优化后的胶束能够随着时间以浓度依赖的方式实现药物的持续释放，从而扩大细胞毒性小分子药物的治疗窗口。
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