Development of a fluvastatin-loaded self-nanoemulsifying system to maximize therapeutic efficacy in human colorectal carcinoma cells

Self-nanoemulsifying delivery systems (SNEDs) are one of the most important approaches for increasing the solubilization and absorption of a drug. This study aimed to develop a system using fluvastatin (FLV) in SNEDs with minimum globule size to enhance cellular uptake and induce apoptosis in human colorectal cancer cells (HCT-116). Thirteen formulations of FLV-loaded SNEDs were prepared, analyzed, and optimized with the extreme vertices mixture design. The optimized formulation had globules 88.4 nm in size, and an IC50 of 23.38 +/- 4.2 mu M compared to 52.69 +/- 6.6 mu M for the raw drug. This optimized formulation was evaluated in HCT-116 cells for its cellular uptake, in vitro cytotoxicity, and the induction of apoptosis. The cellular uptake efficiency of FLV-loaded SNEDs was 47.9 +/- 5.6% and 71.7 +/- 10.2% after 2 and 4h incubation times, respectively, which represents a three-fold increase over the raw drug efficiency. Cellular morphology and DNA fragments confirmed potentiation of apoptosis. These results indicate that loading FLV in SNEDs improves its cellular uptake and hence increases cytotoxicity, making this a promising approach for the treatment of patients with colorectal carcinoma.