Development and characterization of novel intranasal in situ thermoreversible ketoprofen-loaded nanoemulgels for the treatment of glioblastoma

Ketoprofen (KET) has been proven effective against glioblastoma. Nevertheless, its hydrophobic nature and susceptibility to degradation upon administration, added to the blood-brain barrier’s low permeability, make its repurposing for brain cancer treatment challenging. Having this in mind, the purpose of this work was to develop KET-loaded in situ thermoreversible nanoemulgels for intranasal nose-to-brain delivery, aiming at increased drug strength and protection, controlled drug release, and improved bioavailability. Formulations containing Capryol® 90, Tween® 80, Transcutol® HP, poloxamer 407, and water were produced through spontaneous emulsification. Formulations’ droplet size, polydispersity index (PDI), zeta potential, pH, rheology, stability, in vitro drug release, and in vitro antitumor efficacy and safety were evaluated. A high drug strength (4 mg/mL), and small (20 - 30 nm) and monodisperse (PDI 0.1 - 0.2) nanodroplets, with slightly negative to neutral zeta potential (-1.5 to -10 mV), were obtained. The nanoemulgels’ also revealed skin adequate pH (≈ 6), nasal cavity temperature’ sol-gel transitions (32 °C), elevated viscosity (13660 - 927302 cP), and high cumulative controlled in vitro drug release (≈ 78 to 93%), following Makoid-Banakar and Weibull kinetic models. Optimized nanoemulgels revealed relevant efficacy against human glioblastoma U87 cells. Therefore, intranasal thermoreversible KET-loaded nanoemulgels were successfully developed, of innovative composition, showing promising results for glioblastoma treatment. Given their high scalability potential, the developed nanoplatforms could be promising candidates for translational applications, and future in vivo assays could further confirm their potential, so that they might one day be considered as an adjuvant or primary treatment for glioblastoma.