Preparation, physical properties, and stability of gambogic acid-loaded micelles based on chitosan derivatives

The objective of this study is to find out an optimized formulation of water insoluble anticancer drug gambogic acid (GA)-loaded chitosan derivatives micelles. After preliminary test, four factors (the amount of N-octyl-O-sulfate chitosan (AOSC), the amount of GA, volume of ethanol, and dialysis temperature) and three levels for each factor that might affect the formation of micelles were selected and arranged in L₉ (3⁴) orthogonal experimental design to optimize the formulation of GA-loaded micelles. To compare each of the micellar formulations quantitatively, an overall desirability function was defined and calculated based on three assessment indices (drug content, loading efficiency, and entrapping efficiency of micelles). The optimized formulation was 8 mg of GA dissolved in 0.3 mL of ethanol, 12 mg of AOSC dissolved in 2 mL of H₂O, respectively. The drug solution and blank micellar solution were mixed, followed by dialysis against water at 25°C. The mean size of micelle was 100 nm approximately. Lyophilized samples could keep stable for at least 2 months when it was stored at 4°C. These data suggest that the amphiphilic chitosan derivative may improve the water solubility of GA and thus be used as its nano-carrier.