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

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.