HDAC Inhibitor Conjugated Polymeric Prodrug Micelles for Doxorubicin Delivery.
HDAC Inhibitor Conjugated Polymeric Prodrug Micelles for Doxorubicin Delivery.
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DOI：
10.1039/c6tb03038f
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发表时间：
2017-03-21
期刊：
影响因子：
--
通讯作者：
Stefan MC
中科院分区：
文献类型：
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作者：
Senevirathne SA;Washington KE;Miller JB;Biewer MC;Oupicky D;Siegwart DJ;Stefan MC
以聚乙二醇（PEG）为大分子引发剂，通过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，合成了含组蛋白去乙酰化酶抑制剂（HDACi）的两亲性嵌段共聚物。这些两亲性嵌段共聚物自组装成稳定的前药胶束，并表现出良好的生物相容性。实现了高达5.1重量%的多柔比星（DOX）的高负载。优化的胶束能够以浓度依赖性方式随时间持续释放药物，以扩大细胞毒性小分子药物的治疗窗口。报道了携带组蛋白脱乙酰酶抑制剂（HDACi）（4-苯基丁酸和丙戊酸）的两亲性二嵌段共聚物用于胶束药物递送。
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. Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) are reported for micellar drug delivery.