Response surface optimization of self nano-emulsifying drug delivery system of rosuvastatin calcium for hepatocellular carcinoma

Abstract

Purpose: Rosuvastatin calcium (RSC) is a statin which, in addition to its anti-hypercholesteremic effects, was found to have a potential anticancer activity. The target of the present study is to develop self nano-emulsifying drug delivery systems (SNEDDS) loaded with RSC to overcome its poor solubility, and augment its anticancer activity. Methods: A combined mixture-process experimental design was chosen for the optimization of SNEDDS by changing its mixture and process components, where the mixture components were the percentage of Smixture (surfactant and co-surfactant) (X1) and the percentage of oil (X2). The process components were the ratio of surfactant to co-surfactant (X3), and the type of surfactant (X4). Twenty-four formulae were evaluated for % transmittance and saturated solubility. Results: The optimized formula (O1) was selected based on the highest % transmittance and highest drug solubility, where the % transmittance was 99.05 ± 0.09% and the saturated solubility was 80.52 ± 2.57 mg/ml. The optimized formula has a globule size of 17.53 ± 0.89 nm, a zeta potential of − 10.2 ± 0.21 mV, and a cloud point of 88.5 ± 0.54 °C. Transmission electron microscopy demonstrated spherical droplet morphology. In vitro drug release showed remarkable increase in the drug release from the optimized formula as compared to the corresponding standard RSC. The anticancer activity of O1 was evaluated in HepG2 cell-line, where the IC50 value was 16.2 ± 0.23 μg/ml. The optimized formula increased cell death by both apoptosis and necrosis. Conclusion: Our results show that the optimized SNEDDS formula is promising for enhancing the anticancer effect of RSC. © 2020, The Korean Society of Pharmaceutical Sciences and Technology