Anti-inflammatory drug repurposing in skin diseases: ketoprofen-loaded nanoemulsion development and characterization for topical administration

Background the repurposing of non-steroidal anti-inflammatory drugs like ketoprofen (KET) has shown significant potential in melanoma treatment, with previously demonstrated anticancer properties. However, KET's low water solubility hinders its formulation at high concentrations. Objective to overcome this challenge, KET-loaded oil-in-water nanoemulsions were developed and optimized, for the topical treatment of melanoma. Methods formulations containing hydrophobic surfactants Capryol® 90, Lauroglycol 90, or Plurol® Diisostearique, hydrophilic surfactant Tween® 80, and cosurfactant/cosolvent Transcutol® were developed using spontaneous emulsification, and characterized in what concerned droplet size, polydispersity index (PDI), zeta potential, pH, stability, in vitro drug release, ex vivo drug permeation, and in vitro therapeutic efficacy and safety assessment. Key results optimized formulations achieved a high drug loading, small (139.1-170.5 nm) and reasonably homogeneous (PDI 0.240-0.292) droplet sizes, neutral zeta potential (−6.38 to - 9.40 mV), and a skin compatible pH (around 4). Additionally, a controlled and high cumulative in vitro drug release was achieved for selected compositions, with biphasic characteristics (initial burst release followed by a more sustained release), as well as effective ex vivo skin permeation and retention, and good real-time stability. Optimized nanoemulsions significantly reduced B16.F10 murine melanoma cell viability in in vitro cytotoxicity assays, having an enhanced effect when compared to the free drug. Conclusion therefore, novel KET-loaded nanoemulsions were successfully developed, combining drug repurposing and a relevant scalability potential. Future research should explore these nanoplatforms' potential in in vivo models, investigating the possible synergy when combined with UVA radiation.