title: Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles.
abstract: For developing aqueous formulation and improving anti-tumor activity of curcumin (Cur), we prepared Cur encapsulated MPEG-PCL micelles by solid dispersion method without using any surfactants or toxic organic solvent. Cur micelles could be lyophilized into powder form without any cryoprotector or excipient, and the re-dissolved Cur micelles are homogenous and stable. Molecular modeling study suggested that Cur tended to interact with PCL serving as a core embraced by PEG as a shell. After Cur was encapsulated into polymeric micelles, cytotoxicity and cellular uptake were both increased. Cur micelles had a stronger inhibitory effect on proliferation, migration, invasion, and tube formation of HUVECs than free Cur. Besides, Cur micelles showed a sustained in vitro release behavior and slow extravasation from blood vessels in transgenic zebrafish model. Embryonic angiogenesis and tumor-induced angiogenesis were both dramatically inhibited by Cur micelles in transgenic zebrafish model. Furthermore, Cur micelles were more effective in inhibiting tumor growth and prolonged survival in both subcutaneous and pulmonary metastatic LL/2 tumor models. In pharmacokinetic and tissue distribution studies, Cur micelles showed higher concentration and longer retention time in plasma and tumors. Our findings suggested that Cur micelles may have promising applications in pulmonary carcinoma therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. chygong14@yahoo.com.cn
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
authors.forename: Senyi
authors.initials: S
authors.lastname: Deng
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.forename: Xiawei
authors.initials: X
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Bilan
authors.initials: B
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Yishan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D020341:Absorbable Implants; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D008823:Micelles; D053769:Nanocapsules; D003474:Curcumin