Thymoquinone-loaded proposomal film-forming gel for psoriasis: Formulation, characterization and in vivo evaluation

Background: Psoriasis is a persistent autoimmune dermatological ailment Thymoquinone (TQ), shows promising dermatopharmacological effects but suffers from poor skin penetration. To overcome this, TQ was encapsulated in proposomes containing propylene glycol as a permeation enhancer. These were incorporated into a film-forming gel (FFG) to enhance stability, provide sustained release, and form a protective barrier over the skin. Methods: TQ-loaded proposomes (TQP) were prepared using a hot microemulsion technique and optimized via a central composite design. The formulation was evaluated for particle size, polydispersity index (PDI), zeta potential, morphology, and entrapment efficiency. TQP-Opt was then added to an FFG base containing PVA, PVP, and Carbopol 940. The final TQP-Opt FFG was assessed for physical-chemical properties, ex vivo skin permeation, and in vivo antipsoriatic efficacy. Results: The optimized TQP-Opt showed a particle size of 128.1 ± 4.2 nm, PDI of 0.381 ± 0.01, and zeta potential of –20.3 ± 1.1 mV. Entrapment efficiency of TQ in TQP-Opt was 82.0 ± 0.78 % and TQ content in TQP-Opt-FFG was 86.86 ± 0.30 %. The TQP-Opt-FFG was homogeneous and viscous, with sustained drug release of 81.27 ± 1.65 % of TQ over 24 h, following Higuchi's release kinetics. Ex vivo studies showed that the permeation of TQP-Opt-FFG, which is significantly higher than that of the TQ solution (p < 0.001). In vivo preclinical studies demonstrated superior therapeutic efficacy in reversing psoriatic symptoms compared to marketed formulations (p < 0.01) in the Imiquimod (IMQ) induced psoriasis model in mice. The formulation was non-irritant and remained unchanged for three successive months. Conclusion: The TQP-loaded film-forming gel offers a promising, stable, and effective topical strategy for managing psoriasis, with enhanced skin penetration and sustained release.