Development of New Xanthan-Aldehyde/Gelatin Nanogels for Enhancement of Ibuprofen Transdermal Delivery: In-Vitro/Ex-Vivo/In-Vivo Evaluation

The aim of this study was to prepare nanogels based on gelatin and xanthan-aldehyde for the enhancement of ibuprofen transdermal delivery. Firstly, the process of formulating nanogels using the reaction of Schiff’s base was optimized using experimental designs. Secondly, the structural characterization of nanogels was performed using laser particle size, zetometry, FTIR (Fourier Transform Infrared Spectroscopy), XRD (X-Ray Diffraction), SEM (scanning electron microscopy), and thermogravimetric analysis. Finally, the evaluation of pharmacological characteristics and formulation therapeutic efficacy were achieved using in vitro dissolution kinetics, ex vivo transdermal diffusion studies, and an evaluation of in vivo anti-inflammatory activity. The results of the experimental plan show that the formulations containing a ratio of 15:10 ibuprofen/polymer and a ratio of 1:2 gelatin/xanthan-aldehyde with a gelling time of 2 h exhibited the best results; the formulations showed a mean diameter of 179.9 ± 6.2 nm, a polydispersity index of 0.193, which confirms monodispersed particles, a zeta potential of 24.7 mV, denoting a high degree of particle stability, and an encapsulation rate of 93.78%. The FTIR spectroscopy analysis showed the formation of imine function in the nanogel, and scanning electron microscopy showed the globular and porous form of the formulation. The incorporation of ibuprofen into nanogels improved their in vitro dissolution kinetics and ex vivo transdermal diffusion. The incorporation of nanogels into a patch system for its in vivo anti-inflammatory activity has shown excellent efficiency with a percentage of edema inhibition at a dose of 25 mg and 50 mg of 38.77 ± 1.6% and 82.03 ± 9.03%, respectively, while the commercial reference gel presented inhibition values at a dose of 25 mg and 50 mg of 10.61 ± 1.71% and 37.03 ± 11.43%, respectively. Thus, the innovative pharmaceutical form of ibuprofen offers a promising model for enhancing drug bioavailability and therapeutic effects while reducing adverse effects.