Anti-inflammatory drug repurposing for intranasal delivery: ketoprofen nanoemulgel development for the treatment of glioma

The anti-inflammatory drug ketoprofen has shown promising results in the field of drug repurposing for the treatment of brain cancer, but currently developed formulations are for invasive administration (intravenous) and have very limited drug strength. Hence, the purpose of this work was to develop an intranasal oil-in-water nanoemulgel, with drug strength maximization, for non-invasive, more effective and safer treatment of glioma. The developed formulations were made of Capryol® 90 (hydrophobic surfactant), Tween® 80 (hydrophilic surfactant), Transcutol® (co-solvent and permeation enhancer), Pluronic® F-127 (surfactant and gelling agent) and ketoprofen. Droplet size, polydispersity index, in vitro drug release and accelerated stability were measured. Results showed that the addition of Pluronic to a preliminary optimized nanoemulsion led to a significant droplet size and PDI reduction (176 to 22 nm, and 0.3 to 0.1, respectively). Achieved drug strength was 4 mg/mL, which is more than 50 times higher than ketoprofen’s aqueous solubility. The developed formulations also appeared to have high stability, with instability indexes between 0.130 and 0.265, and high cumulative drug release percentage, varying between 78 to 93% after 24h. Formulations also showed a controlled release profile, fitting a Korsmeyer-Peppas kinetic model, with low AIC (43.84 to 54.67) and high R² (0.9725 to 0.9971) values, depicting non-Fickian diffusion (n between 0.7 and 0.8). Hence, high drug strength, high stability and high drug release ketoprofen-loaded nanoemulgels were successfully prepared. Future in vitro cytotoxicity evaluation in glioma cells will assess the true potential of the developed formulations for the treatment of brain cancer.