Preparation and In vitro/In vivo Evaluation of Fingolimod hydrochloride Loaded Polymeric Mixed Nano-Micelles for Treatment of Multiple Sclerosis.

Abstract

Fingolimod (FYN) is one of the approved medicines for treatment of multiple sclerosis (MS) while exhibiting several side effects such as liver enzyme elevation and cardiac damage. This study was aimed to prepare the mixed micelles of ascorbyl palmitate (AP) and alpha-tocopherol polyethylene glycol succinate (TPGS) as a delivery system for FYN. The mixed micelles were prepared by thin film hydration method at different ratios of AP/TPGS. Saturation solubility of the micelles was compared with the pure drug. The optimized formulation was characterized by scanning electron microscopy (SEM) and subjected for stability study at 5 ± 3 °C for 3 months. The effect of the prepared fingolimod loaded micelles (FYN-Micelle) was finally assessed by experimental autoimmune encephalomyelitis (EAE) model at the dose of 0.3, 1, and 3 mg/kg of fingolimod, which was administrated intraperitoneally. The results indicated that the prepared mixed micelles at the AP/TPGS ratio of 1:5 showed a particle size, zeta potential, and an entrapment efficiency of 116.86 ± 2.41 nm, 23.61 ± 4.56 mV, and 63.28 ± 5.31%, respectively. Also, this formulation was stable after a 3-month incubation at 5 ± 3 °C. SEM images displayed an amorphous state of the drug in the micelles. Animal studies confirmed that this formulation at the dose of 1 mg/kg could enhance the myelin density of the brain while reducing cardiac and hepatic impairment. Therefore, these findings suggested that FYN-Micelle could be exploited as an effective delivery system for fingolimod hydrochloride to treat MS.