Folic acid‐modified nonionic surfactant vesicles for gambogenic acid targeting: Preparation, characterization, and in vitro and in vivo evaluation

Abstract

Abstract The aim of present study was to develop folic acid (FA)‐modified nonionic surfactant vesicles (NISVs, niosomes) as carrier systems for targeted delivery of gambogenic acid (GNA). The FA‐GNA‐NISVs exhibited a mean particle size of 180.77 ± 2.41 nm with a narrow poly dispersion index of 0.147 ± 0.08 determined by dynamic light scattering. Transmission electron microscopy also revealed that the FA‐GNA‐NISVs were spherical with double‐layer structure. Entrapment efficiency (EE%) and zeta potential of the optimal FA‐GNA‐NISVs were 87.84 ± 1.06% and −37.33 ± 0.33 mV, respectively. Differential scanning calorimetry demonstrated that the GNA was in a molecular or amorphous state inside the FA‐NISVs in vitro release profiles suggested that FA‐GNA‐NISVs could release GNA at a sustained manner, and less than 60% of GNA was released from the FA‐NISVs within 12 hours of dialysis. in vivo pharmacokinetic results illustrated that FA‐GNA‐NISVs had considerably higher Cmax, area under curve (AUC0 − t) and accumulation in lung. The cell proliferation study shown that the FA‐GNA‐NISVs significantly enhanced the in vitro cytotoxicity against A549 cells. Flow cytometry and fluorescence microscopy further demonstrated that the FA‐GNA‐NISVs increased apoptosis compared with nonmodified GNA‐NISVs and free GNA. Moreover, FA‐GNA‐NISVs induced A549 cell apoptosis in a dose‐dependent manner. In addition, cellular uptake assays showed a higher uptake of FA‐GNA‐NISVs than GNA‐NISVs as well as free GNA. Taken together, it could be concluded that FA‐GNA‐NISVs were proposed as a novel targeting carriers for efficient delivering of GNA to cancers cells.

Keywords

• folic acid
• gambogenic acid
• nonionic surfactant vesicles
• targeted delivery