Repurposing verapamil hydrochloride with niosomal gel technology: Enhanced efficacy and skin penetration in hypertrophic scars

Abstract

Hypertrophic scars arising from abnormal wound healing after burns, trauma, or surgery present challenges for their effective treatment. Verapamil hydrochloride (VHCl), a calcium channel blocker primarily used in cardiovascular diseases, has been proposed as a niosomal gel for topical hypertrophic scar treatment. VHCL stimulates procollagenase synthesis, induces actin filament depolymerization, and reduces fibrous tissue production, thus making it a promising candidate for scar therapy. Prior to formulation, FT-IR spectroscopy was performed to assess drug and excipient compatibility. VHCl niosomes were prepared using the thin-film hydration technique with Span-40 and cholesterol in a 7:3 molar ratio. The characterization included entrapment efficiency (%EE), vesicle size, and surface morphology. Optimized niosomes were incorporated into a gel, and in in-vitro drug release and stability studies were conducted. An in-vivo study was conducted using a rabbit model to assess formulation efficacy. Optimized VHCl niosomal formulations with high entrapment efficiency (%EE) of 71.62 % and a small vesicle size of 180 nm were used for characterization, in-vitro and in-vivo evaluations. The vesicles displayed a monodisperse distribution, spherical and irregular morphology under TEM, and good stability for 60 days at room and refrigerated temperatures. The lyophilized formulation incorporated into the silicone gel exhibited optimal pH, thixotropic rheological behavior, and sustained VHCl release for up to 48 h. In-vivo studies on a rabbit ear model revealed enhanced efficacy, reducing hypertrophic scar diameter from 7 mm to 1.9 mm after 28 days. The combination of VHCl-loaded niosomal gels demonstrated improved permeation and synergistic effects, enhancing the safety and efficacy of long-term VHCl treatment.