Preparation and characterization of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles for the solubilization and in vivo delivery of luteolin

Jin-Feng Qiu,¹ Xiang Gao,^1,2 Bi-Lan Wang,¹ Xia-Wei Wei,¹ Ma-Ling Gou,¹ Ke Men,¹ Xing-Yu Liu,¹ Gang Guo,¹ Zhi-Yong Qian,¹ Mei-Juan Huang<sup>1

1</sup>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; ²Medical School and Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People’s Republic of China

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(ε-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 (t_½; 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.

Keywords: luteolin, micelle, MPEG-PCL, cancer therapy