title: Preparation and characterization of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles for the solubilization and in vivo delivery of luteolin.
abstract: Luteolin (Lu) is one of the flavonoids with anticancer activity, but its poor water solubility limits its use clinically. In this work, we used monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles to encapsulate Lu by a self-assembly method, creating a water-soluble Lu/MPEG-PCL micelle. These micelles had a mean particle size of 38.6 ± 0.6 nm (polydispersity index = 0.16 ± 0.02), encapsulation efficiency of 98.32% ± 1.12%, and drug loading of 3.93% ± 0.25%. Lu/MPEG-PCL micelles could slowly release Lu in vitro. Encapsulation of Lu in MPEG-PCL micelles improved the half-life (t½ ; 152.25 ± 49.92 versus [vs] 7.16 ± 1.23 minutes, P = 0.007), area under the curve (0-t) (2914.05 ± 445.17 vs 502.65 ± 140.12 mg/L/minute, P = 0.001), area under the curve (0-∞) (2989.03 ± 433.22 vs 503.81 ± 141.41 mg/L/minute, P = 0.001), and peak concentration (92.70 ± 11.61 vs 38.98 ± 7.73 mg/L, P = 0.003) of Lu when the drug was intravenously administered at a dose of 30 mg/kg in rats. Also, Lu/MPEG-PCL micelles maintained the cytotoxicity of Lu on 4T1 breast cancer cells (IC50 = 6.4 ± 2.30 μg/mL) and C-26 colon carcinoma cells (IC50 = 12.62 ± 2.17 μg/mL) in vitro. These data suggested that encapsulation of Lu into MPEG-PCL micelles created an aqueous formulation of Lu with potential anticancer effect.
authors.affiliation: Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Qiu
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Bi-Lan
authors.initials: BL
authors.lastname: Wang
authors.forename: Xia-Wei
authors.initials: XW
authors.lastname: Wei
authors.forename: Ma-Ling
authors.initials: ML
authors.lastname: Gou
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Qian
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047311:Luteolin / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D047311:Luteolin
keywords: MPEG-PCL; cancer therapy; luteolin; micelle