Formulation, development and in vivo characterization of selegiline hydrochloride nanostructured lipid nanocarrier loaded microneedle array patch for depression.

Depression is a common mental condition causing depressed mood and loss of pleasure. The primary treatment approach for the management of depression consists of the use of selegiline (MAO-B) inhibitor compound. The present work aimed to develop and optimize selegiline-loaded nanostructured lipid carriers for transdermal application, utilizing a 2 full factorial design approach. The optimized nanostructured lipid carriers formulation (Batch B7) demonstrated a particle size of 158.71 ± 0.56 nm, a narrow size distribution (0.266 ± 0.006), high entrapment efficiency (59.60 ± 0.34 %), and a zeta potential of -23.2 ± 2.21 mV. Furthermore, x-ray diffraction and differential scanning calorimetry studies revealed the amorphous transformation of selegiline within the nanostructured lipid carrier. Transmission Electron Microscopy study has shown that nanostructured lipid carrier particles had a spherical shape with a smooth surface. These optimized nanostructured lipid carriers were then incorporated into a microneedle array patch for transdermal delivery. The selegiline-loaded nanostructured lipid carrier microneedle array patch exhibited no skin irritation in a rabbit model. It enhanced drug diffusion ex vivo (1.13-fold compared to pure selegiline-loaded microneedle array patch) with 90 % drug release in 12 h. The pharmacokinetic study demonstrated a steady and controlled release profile with a half-life of 29.9 ± 0.14 h and AUC (26.57 ± 0.51 μg/ml*h) of selegiline loaded nanostructured lipid carrier microneedle array patch. On the contrary, a pure selegiline-loaded microneedle array patch showed a short half-life of 6.5 ± 0.26 h and AUC (20.90 ± 0.31 μg/ml*h). The sustained release profile and prolonged half-life in plasma and the brain suggest improved therapeutic efficacy. Histopathology analysis revealed no significant toxicity to vital organs. Thus, a selegiline nanostructured lipid carrier-loaded microneedle array patch can increase brain bioavailability compared to a pure selegiline-loaded microneedle array patch for managing depression.