Dermatopharmacokinetic and pharmacodynamic evaluation of a novel nanostructured formulation containing capsaicinoids for treating neuropathic pain.

The in vivo skin penetration by dermal microdialysis and the pharmacological efficacy of a chitosan hydrogel containing capsaicinoids-loaded nanocapsules (CHNC) was evaluated in this study. Such gel has previously been proven to control capsaicinoids release and decrease the drugs side effects in humans. The nanocapsules containing capsaicinoids had an average size around 150 nm, with a low polydispersity index, positive zeta potential, and high encapsulation efficiency of the drugs. The CHNC showed intact nanocapsules, a slightly acid pH value, and a pseudoplastic behavior suitable for topical application. Microdialysis experiments showed a 1.6-fold increase in the concentration of capsaicinoids in the dermis (after 12 h of its application) when CHNC was administered compared to a chitosan hydrogel containing capsaicinoids in hydroethanolic solution (CHET) and the commercial cream. The CHNC showed antiallodynic and antihyperalgesic effects from 6 h to 96 h after treatment initiation, whereas CHET and the commercial cream showed antiallodynic and antihyperalgesic effects only at 48 h and 96 h after treatment initiation, respectively. CHNC and the commercial cream maintained antihyperalgesic activity for 6 days after treatment interruption. For mechanical allodynia, the antinociceptive effect was maintained for 48 h after treatment interruption only with CHNC. In conclusion, CHNC is a promising formulation for treating peripheral neuropathic pain.