title: Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo.
abstract: Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: MaLing
authors.initials: M
authors.lastname: Gou
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.forename: HuaShan
authors.initials: H
authors.lastname: Shi
authors.forename: MingLi
authors.initials: M
authors.lastname: Xiang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: JianLin
authors.initials: J
authors.lastname: Long
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Qian
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008823:Micelles; D011108:Polymers; D003474:Curcumin