Hexosomes as Efficient Platforms for Possible Fluoxetine Hydrochloride Repurposing with Improved Cytotoxicity against HepG2 Cells

The aim of this study was to investigate the feasibility of hexosomes (HEXs) as competent platforms for fluoxetine hydrochloride (FH) repurposing against HepG2 hepatocellular carcinoma. Different FH-loaded HEX formulations were prepared and optimized by the hot emulsification method. The HEX features such as particle size, ζ potential, and drug entrapment efficiency (EE%) can be tailored by tuning HEX components and fabrication conditions. The composition of the optimized FH hexosome (OFH-HEX) was composed of 3.1, 1.4, 0.5, 0.2, and 94.8% for glyceryl monooleate, oleic acid, pluronic F127, FH, and deionized water, respectively. The anionic OFH-HEX with a particle size of 145.5 ± 2.5 nm and drug EE% of 45.4 ± 1.2% was able to prolong the in vitro FH release, where only 19.5 ± 2.3% released in phosphate-buffered saline (PBS) pH 7.4 after 24 h. Contrarily, HEX rapidly released FH in acetate buffer pH 5.5 and achieved a 90.5 ± 4.7% release after 24 h. The obtained HEX showed an improved cellular internalization in a time-dependent manner and enhanced the cytotoxicity (2-fold higher than FH solution). The current study suggests the potential of FH-HEX as a possible anticancer agent against hepatocellular carcinoma.