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Preparation of Icaritin-Loaded mPEG-PLA Micelles and Evaluation on Ischemic Brain Injury.
Journal of Biomedical Nanotechnology 2019 April 2
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 μ g/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 μ g/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.
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