Exploring topical atorvastatin hyalurosomal gel as an adjuvant for reducing systemic corticosteroid dosage: a randomized clinical trial in severe oral lichen planus patients.

Oral lichen planus (OLP) is a chronic inflammatory disorder with limited topical treatment options and long-term corticosteroid dependency. This study investigates a novel atorvastatin-loaded hyalurosomal gel (ATV-Hyalugel) as a topical adjuvant to reduce systemic corticosteroid use in severe OLP. The objective of the study is to develop, optimize, characterize ATV-Hyalugel and evaluate its clinical efficacy in a randomized controlled clinical trial. ATV-loaded hyalurosomes (ATV-HAs) were prepared via thin-film hydration and optimized using an I-optimal mixture design (independent variables: phospholipid, Tween 80, and hyaluronic acid; responses: entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimal formulation was incorporated into a chitosan gel, which was characterized for its pH, rheological behavior, and in-vitro drug release. Four weeks randomized controlled trial (n = 90) compared: group one received standard prednisolone (40 mg/day) while group two received half-dose prednisolone (20 mg/day) in combination with ATV-Hyalugel (topically, three times daily). Pain and ulcer scores were recorded weekly. Between-group comparisons were performed using the Mann-Whitney U test (non-parametric; α = 0.05), and within-group improvement from baseline to Week 4 was assessed using the Kruskal-Wallis test. Optimized ATV-HAs demonstrated high EE% (79.1 ± 0.4%), uniform PS (221.2 ± 5.1 nm), and stable ZP (-31.6 ± 0.2 mV). ATV-Hyalugel exhibited mucosa-compatible pH (6.48 ± 0.2), pseudoplastic rheology, and a sustained release profile dominated by diffusion-driven kinetics. Clinically, group two achieved therapeutic equivalence to group one by Week 2 (p > 0.05), despite receiving 50% less corticosteroid. Both groups showed significant symptom reduction from baseline to Week four (p < 0.0001, Kruskal-Wallis). No adverse events were reported with ATV-Hyalugel. ATV-Hyalugel enables a 50% corticosteroid dose reduction while maintaining clinical efficacy. Its favorable release kinetics and safety profile support its use as an innovative adjuvant therapy for severe OLP.