Development of etoricoxib-loaded mesoporous silica nanoparticles laden gel as vehicle for transdermal delivery: optimization, ex vivo permeation, histopathology, and in vivo anti-inflammatory study

Objective: Etoricoxib (ETB) is a nonsteroidal anti-inflammatory therapeutic agent. It is poorly soluble and has various gastrointestinal side effects such as bleeding and ulcers after oral administration. The present research aimed to develop an ETB-loaded mesoporous silica nanoparticle-laden gel (ETB-MSNPs) for transdermal delivery to improve therapeutic efficacy. Methods: The ETB-MSNPs were synthesized using a precipitation and solvent evaporation technique and their optimization was performed using a Box–Behnken design. The optimized ETB-MSNPs were incorporated into a carbopol–chitosan gel and evaluated for in vitro, ex vivo, and in vivo anti-inflammatory activity. Results: The ETB-MSNPs displayed nanosize of particles with nanosize distribution and high entrapment efficiency of ETB. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies showed that ETB was encapsulated in MSNPs. The optimized ETB-MSNPs were successfully integrated into the carbopol and chitosan gel, which exhibited excellent viscosity and spreadability. The optimized ETB-MSNPs gel exhibited a significantly higher and more sustained release of ETB compared to pure ETB gel. Optimized ETB-MSNPs gel exhibited a considerably higher anti-inflammatory effect with a significant reduction in IL-1β and TNF-α levels compared to pure ETB gel. The histopathological examination confirmed that optimized ETB-MSNPs gel did not exhibit any toxicity on the skin. Conclusion: Based on the findings, the results suggest that the MSNPs gel has the potential as a carrier for enhancing the therapeutic efficacy of ETB through topical delivery, although further studies are needed to fully confirm its effectiveness.