Injected laquinimod D-α-tocopheryl polyethylene glycol-1000 succinate polymeric micelles for the treatment of inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Laquinimod (LAQ), a poorly water-soluble compound, was proved to be effective for colitis remission at low dose of 0.5 mg/kg in patients with Crohn's disease. Due to its extremely low solubility in water, it was difficult to develop an injectable liquid dosage form. Herein, D-α-Tocopheryl polyethylene glycol-1000 succinate (TPGS) polymeric micelles were developed as a delivery vehicle of LAQ for the management of inflammatory bowel disease. Using the LAQ/TPGS ratio of 1:100, LAQ-loaded micelles were successfully prepared by thin-film dispersion method. The solubility of LAQ in water was significantly increased from 10.5 μg/mL in pure water to 500 μg/mL in TPGS micelles. LAQ-loaded micelles of TPGS exhibited the fine particle size of 34.6 nm and Zeta potential of -0.67 mV. Moreover, the good stability of LAQ-loaded micelles in physiology-mimicking medium was confirmed by detecting their particle size, zeta potential and leakage of the loading drug. Therapeutic effect of LAQ-loaded micelles on DSS-induced mice was proved by detecting DAI score, colon length and loss of body weight. Moreover, the morphology and colonic mucosal barrier of the injured colon of DSS-induced mice was largely recovered after treatment with LAQ-loaded micelles. Meanwhile, the inflammation of colitis colon was also obviously alleviated by LAQ-loaded micelles. Conclusively, polymeric micelles of TPGS may be a promising delivery vehicle of LAQ for the management of inflammatory bowel disease.