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

• Psoriasis is a chronic skin condition with excessive keratinocyte proliferation. • Thymoquinone helps treat psoriasis with its anti-inflammatory and antioxidant effects. • Topical use of thymoquinone is limited due to its low solubility and skin permeability. • Proposome with propylene glycol as permeation enhancer addresses these drawbacks. • Film-forming gel forms a protective layer on the skin, promoting sustained release. • Film-forming gel containing thymoquinone proposomes may improve psoriasis management through targeted delivery. Psoriasis is a persistent autoimmune dermatological ailment marked by significant health complications arising from excessive keratinocyte proliferation with inadequate differentiation. Conventional topical treatments often cause adverse effects, leading to poor patient compliance. Thymoquinone (TQ), a bioactive benzoquinone, shows promising dermatopharmacological effects but suffers from poor skin penetration. To overcome this, TQ was encapsulated in nanosized proposomes (128–150 nm) 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. 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. 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. The TQP-loaded film-forming gel offers a promising, stable, and effective topical strategy for managing psoriasis, with enhanced skin penetration and sustained release.