Development of self-nanoemulsifying drug delivery system of 1-(2, 5-dihydroxy phenyl)-3-pyridine-2-yl-propenone to enhance pro-apoptotic activities in MCF-7 breast cancer cells

Abstract

Compound 1-(2, 5-dihydroxy phenyl)-3-pyridine-2-yl-propenone is a derivative of 2′, 5′-dihydrochalcone, with a 2-pyridine substitution in B ring. Several studies showed that it is an effective anti-inflammatory and anticancer agent. However, its low water solubility limits its therapeutic applications and bioavailability. Therefore, 1-(2, 5-dihydroxy phenyl)-3-pyridine-2-yl-propenone was formulated into self-nano-emulsifying drug delivery systems (SNEDDS), to improve its solubility and bioavailability. A total of three formulas, F1 (10%:67.5%:22.5%), F2 (15%:63.75%:21.25%), and F3 (20%:60%:20%) were developed with variation in olive oil as the oil phase, tween 80 and PEG 400. The optimal formula was determined based on the droplet size, polydispersity index (PDI), and emulsification time. It was then further evaluated for its zeta potential, drug loading capacity, and cytotoxic activity toward MCF7 cells using [3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium-bromide] assay. Among the three formulations, F1 produced more suitable physicochemical characteristics, such as a low droplet size of 11.06 ± 0.06 nm, PDI of 0.10 ± 0.02, and ability to self-emulsify into nanoemulsion within 10.51 ± 0.45 seconds. It also had a good zeta potential of −16.24 ± 2.40 mV with a maximum loading capacity of 6 mg drug per 1 g of SNEDDS. The IC50 toward MCF7 cells for F1 was 5.3 µg/ml which shows moderate cytotoxic activity. It also modified the cells’ morphology which led to a decrease in cancer cells’ viability. Based on these results, SNEDDS 1-(2, 5-dihydroxy phenyl)-3-pyridine-2-yl-propenone has been successfully formulated and potential as a carrier that is effective against MCF7 cells.