Novel transethosomes for the delivery of brucine and strychnine: Formulation optimization, characterization and in vitro evaluation in hepatoma cells

Nux vomica has been used in China as a traditional medicine for treatment of liver cancer, but its clinical use is limited by serious side-effects. Studies have shown that brucine and strychnine are the main active components of nux vomica. The objective of this research was to develop a transdermal brucine-strychnine transethosome (BS-TE) formulation that could be taken up by hepatoma cells in vitro and inhibit their proliferation. The BS-TE formulation was optimized by central composite design-response surface methodology (CCD-RSM). The average total entrapment efficiency of BS-TE was 92.50% ± 0.0489% and the average total drug loading was 8.63% ± 0.0289%. In vitro release and percutaneous permeation of BS-TE were investigated by dynamic dialysis and Franz diffusion cell methods. Fluorescence microscopy combined with flow cytometry analysis was used to study the in vitro cellular uptake of transethosomes. In addition, MTT assay was used to evaluate in vitro cytotoxicity. The results showed that compared with free brucine and strychnine, BS-TE exhibited better transdermal permeation. The BS-TE formulation was taken up by hepatoma cells in vitro and slowly released the active components to give long-term, potent inhibition of proliferation. This research provides a new approach for the development and clinical application of brucine and strychnine.