Preparation of Icaritin-Loaded mPEG-PLA Micelles and Evaluation on Ischemic Brain Injury

Icaritin is an active ingredient derived from the plant Herba Epimedium, which exhibits various pharmacological and biological activities. However, icaritin has solubility in water of less than 1.0 μg/ml and the low aqueous solubility hampered its use as a therapeutic agent. In this work, as shown in Scheme 1, we synthesized a series of mPEG-PLA (Methyl poly (ethylene glycol)-Polylactic acid) with different hydrophilic and hydrophobic segment ratios via ring-opening polymerization and prepared mPEG-PLA/icaritin micelles by solid dispersion method to improve the solubility of icaritin. After studying the particle size, zeta potential, encapsulation efficiency and drug loading efficiency, mPEG2000-PLA50(hydrophilic/hydrophobic segment ratio = 5:6) was selected for subsequent experiment, including single factor experiments and orthogonal experiments for optimizing mPEG-PLA (5:6)/icaritin micelles preparation. The particle size and zeta potential of the mPEG-PLA (5:6)/icaritin micelles were about (64.25 ± 0.21) nm and (-1.37 ± 0.31) mV, the encapsulation efficiency (EE) and drug loading efficiency (DL) were 83.96% and 9.33%, the critical micelle concentration was about 2.24 μg/ml and the solubility about 2.0 mg/ml in water. In vivo studies have shown that mPEG-PLA (5:6)/icaritin micelles have a longer circulation time in plasma and have a distribution in the brain of mice. The pharmacodynamic results indicated that pretreatment with mPEG-PLA (5:6)/icaritin micelles can decrease neurological deficit score, diminish the infarct volume and brain edema. These results suggested that mPEG-PLA (5:6)/icaritin micelles have a good advantage to improve the bioavailability of icaritin, potentially to be a neuroprotectant for ischemic brain injury.