Alpinumisoflavone, a major compound in unripe Cudrania tricuspidata fruit is reported\nto exhibit numerous beneficial pharmacological activities, such as osteoprotective, antibacterial,\nestrogenic, anti-metastatic, atheroprotective, antioxidant, and anticancer effects. Despite its medicinal\nvalue, alpinumisoflavone is poorly soluble in water, which makes it difficult to formulate and\nadminister intravenously (i.v.). To overcome these limitations, we used methoxy poly(ethylene\nglycol)-b-poly(d,l-lactide) (mPEG-b-PLA) polymeric micelles to solubilize alpinumisoflavone and\nincrease its bioavailability, and evaluated their toxicity in vivo. Alpinumisoflavone-loaded polymeric\nmicelles were prepared using thin-film hydration method, and their physicochemical properties\nwere characterized for drug release, particle size, drug-loading (DL, %), and encapsulation efficiency\n(EE, %). The in vitro drug release profile was determined and the release rate of alpinumisoflavone\nfrom mPEG-b-PLA micelles was slower than that from drug solution, and sustained. Pharmacokinetic\nstudies showed decreased total clearance and volume of distribution of alpinumisoflavone, whereas\narea under the curve (AUC) and bioavailability were significantly increased by incorporation in\nmPEG-b-PLA micelles. In vivo toxicity assay revealed that alpinumisoflavone-loaded mPEG-b-PLA\nmicelles had no severe toxicity. In conclusion, we prepared an intravenous (i.v.) injectable\nalpinumisoflavone formulation, which was solubilized using mPEG-b-PLA micelles, and determined\ntheir physicochemical properties, pharmacokinetics, and toxicity profiles.
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