Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2–3% of the world population. Current topical treatments, including corticosteroids like hydrocortisone, are limited by adverse effects such as skin atrophy, tachyphylaxis, and rebound phenomenon upon withdrawal. Silk sericin, a natural protein derived from Bombyx mori silkworm cocoons, possesses remarkable moisturizing, antioxidant, anti-inflammatory, and wound-healing properties. However, no formulation has combined sericin with a low-dose corticosteroid for synergistic psoriasis management.

Objective: To formulate, optimize, and evaluate an herbal-insect synergistic topical cream containing silk sericin (2% w/w) and hydrocortisone (0.5% w/w) for improved psoriasis management with reduced steroid-related side effects.

Methods: Silk sericin was extracted from Bombyx mori cocoons using the degumming method (0.5% Na₂CO₃, 95°C, 60 min), followed by dialysis and lyophilization. An oil-in-water (O/W) cream base was prepared using emulsifying wax, liquid paraffin, propylene glycol, and purified water. Four formulations (F1–F4) were developed with varying sericin concentrations (0.5%, 1%, 2%, 2.5%) and fixed hydrocortisone (0.5% w/w). Formulations were evaluated for physicochemical parameters (pH, viscosity, spread ability, homogeneity, extrudability, phase separation), stability under accelerated conditions (40°C/75% RH for 3 months), and in vitro drug release using Franz diffusion cell. In vivo ant psoriatic activity was assessed using the imiquimod (IMQ)-induced psoriasis-like dermatitis model in BALB/c mice (n=6 per group) over 7 days. Groups included: normal control, IMQ control, vehicle cream, hydrocortisone 0.5% cream, sericin 2% cream, and synergistic cream (sericin 2% + hydrocortisone 0.5%). Psoriasis Area Severity Index (PASI) score, ear thickness, spleen weight, histopathology (H&E staining), immunohistochemistry (Ki-67, PCNA), and cytokine levels (IL-17, IL-23, TNF-α) were evaluated.

Results: The optimized formulation (F3: 2% sericin + 0.5% hydrocortisone) showed desirable properties: pH 6.2 ± 0.2 (compatible with skin), viscosity 18,450 ± 450 cP, spread ability 9.2 ± 0.3 g·cm/s, extrudability 92%, and no phase separation after 3 months of accelerated stability. In vitro drug release followed Higuchi kinetics (R² = 0.982) with 78.4% of hydrocortisone released over 8 hours. In the IMQ-induced psoriasis model, the synergistic cream significantly reduced PASI score (2.1 ± 0.3 vs IMQ control 7.8 ± 0.4, p<0.001), ear thickness (0.28 ± 0.02 mm vs 0.52 ± 0.03 mm, p<0.001), and spleen weight (0.12 ± 0.01 g vs 0.24 ± 0.02 g, p<0.001) compared to IMQ control. The synergistic cream was superior to either hydrocortisone alone (PASI 4.2 ± 0.3) or sericin alone (PASI 5.1 ± 0.4) (p<0.05). Histopathology showed marked reduction in epidermal thickness (acanthosis), parakeratosis, and inflammatory infiltration in the synergistic cream group. Immunohistochemistry revealed reduced Ki-67 and PCNA expression, indicating decreased keratinocyte proliferation. Cytokine analysis showed significant reduction in IL-17 (78% decrease), IL-23 (65% decrease), and TNF-α (70% decrease) compared to IMQ control.