Development and Evaluation of Lycopene and Alpha-Tocopherol-Loaded Ethosomal Gel Optimized by Design of Experiments for Managing Oral Sub-Mucosal Fibrosis

Abstract

Background: Oral sub-mucosal fibrosis (OSMF) is a chronic fibro-inflammatory disorder marked by progressive fibrosis leading to collagen deposition in the epithelial layer of the mouth. Trismus and dysfunction may result from an effect on the underlying masticatory muscles. Ethosomes were fabricated using a cold method. Aim: This research focused on the formulation of a novel ethosomal gel encapsulating lycopene, which exhibits both antioxidant and anti-inflammatory properties, and Alpha-Tocopherol, a well-known antioxidant, aimed at enhancing localized therapy for OSMF.  Ethosomes are systematically optimized through Design of Experiments (DOE) to fine-tune vesicle size, drug loading, and release behaviour. Result: The optimized ethosomal gel exhibited a pH of 6.5 ± 0.01, good viscosity, and spreadability (1.76 ± 0.03 g·cm/s). It achieved entrapment efficiencies of 85.24% for lycopene and 83.67% for alpha-tocopherol. It provided sustained drug release, indicating suitability for controlled buccal delivery. Cumulative drug release reached 45.53%, 63.03%, and 85.72% (Lycopene) and 21.74%, 42.95%, and 77.13% (Alpha-Tocopherol) at 1, 5, and 24 h, confirming sustained delivery and good vesicle stability.