Brilaroxazine lipogel displays antipsoriatic activity in imiquimod-induced mouse model.

Abstract

Dopamine (D) and serotonin (5-HT) pathways contribute to psoriasis pathobiology. Disruptions incite increased inflammatory mediators, keratinocyte activation and deterioration, and worsening symptoms. Brilaroxazine (RP5063), which displays potent high binding affinity to D2/3/4 and 5-HT1A/2A/2B/7 receptors and a moderate affinity to serotonin transporter (SERT), may affect the underlying psoriasis pathology. An imiquimod-induced psoriatic mouse model (BALB/c) evaluated brilaroxazine's activity in a topical liposomal-aqueous gel (Lipogel) formulation. Two of the three groups (n=6 per) underwent induction with 5% imiquimod, and one group received topical brilaroxazine Lipogel (Days 1-11). Assessments included (1) Psoriasis Area and Severity Index (PASI) scores (Days 1-12), skin histology for Baker score based on H&E stained tissue (Day 12), and serum blood collection for serum cytokine analysis (Day 12). One-way ANOVA followed by post hoc Dunnett's t-test evaluated significance (p<0.05). Imiquimod-induced animal Baker scores were higher versus Sham non-induced control's results (p<0.001). Brilaroxazine Lipogel had significantly (p=0.003) lower Baker scores versus the induced Psoriasis group. Brilaroxazine PASI scores were lower (p=0.03) versus the induced Psoriasis group (Days3-12), with the greatest effect in the last 3 days. The induced Psoriasis group showed higher Ki-67 and TGF-β levels versus non-induced Sham controls (p=0.001). The brilaroxazine Lipogel group displayed lower levels of these cytokines versus the induced Psoriasis group, Ki-67 (p=0.001) and TGF-β (p=0.008), and no difference in TNF-α levels versus Sham non-induced controls. Brilaroxazine Lipogel displayed significant activity in imiquimod-induced psoriatic animals, offering a novel therapeutic strategy.