The aim of this study was to develop a gambogic acid-loaded mixed micelles (GA-M) system, using Kolliphor HS15 and lecithin, for enhancement of oral bioavailability. GA-M was prepared using the thin film hydration method, and particle size and zeta potential indexes were used to determine the optimized formulation was optimized with taking particle size, zeta potential as indexes. The optimal GA-M system had a mean particle size in the nanometer range (87.22 ± 0.68 nm) and zeta potential greater than 20 mV in magnitude (-21.63 ± 1.69 mV) at a 1:1 proportion of HS15: lecithin. Additionally, the carriers had a high entrapment efficiency (98.32 ± 3.52%) and drug loading (4.68 ± 0.17%). Furthermore, the in vitro GA release characteristics followed first-order kinetics, suggesting that the release of the molecule was achieved both by medium diffusion and structural erosion. Transport elucidation in Caco-2 cells demonstrated that the efflux ratio of encapsulated GA was dramatically decreased from 1.42 to 0.76, and pharmacokinetic studies showed that the oral bioavailability of GA-M was 2.3 times higher than that of free GA, indicating that HS15/lecithin mixed micelles could promote absorption in the gastrointestinal tract. Overall, these results present a micelle system suitable for oral delivery, with increased solubility and oral bioavailability of GA.
Keywords: Gambogic acid; bioavailability; design; micelles; pharmacokinetics.