The effective delivery of anti-cancer drugs with minimal side effects and better therapeutic efficacy has remained an active area of research for many decades. Organogels have gained attention in recent years as potential drug delivery systems due to their high bioavailability, no first-pass metabolism and rapid action. Considering this, in the current study an organogel based nanoemulsion was developed aiming to effectively deliver hydrophobic drugs via encapsulation within in situ gellable organogel droplets, termed as gel-in-water (G/W) nanoemulsion. G/W nanoemulsion was prepared using a combination of lipiodol and organogelator 12-hydroxystearic acid (12-HSA) as inner gel phase; dispersed in water by ultrasonication and stabilized with polyoxyethylene hydrogenated castor oil (HCO-60) as a surfactant. The prepared nanoemulsion showed high drug loading efficiency (≈97%) with a mean diameter of 206 nm. Lower polydispersity index (PdI) value (≈0.1) suggests monodispersed nature of G/W nanoemulsion in the continuous phase. G/W nanoemulsion was found stable over six months in terms of particle size, zeta potential and pH at different storage temperatures. There was no cytotoxic effect of prepared G/W nanoemulsion on primary hepatocytes in vitro. In contrast, paclitaxel-loaded G/W showed a significant decrease in melanoma cell growth (*p < 0.05) both in vitro and in vivo. Our results support the hypothesis that organogel based nanoemulsions can be a promising drug delivery system.
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