Chitosan-Based Nanoemulgel for Enhanced Co-Delivery and Sustained Release of Lipophilic Cynaropicrin and Hydrophilic Salicin: Formulation, Physicochemical Characterization, and Stability

Abstract

The co-delivery of therapeutic agents with differing physicochemical properties presents significant formulation challenges. This study aimed to develop and characterize a chitosan-based nanoemulgel for the simultaneous encapsulation and sustained delivery of the lipophilic anticancer agent cynaropicrin and the hydrophilic anti-inflammatory/anticancer agent salicin. Nanoemulsions were prepared by integrating an oil phase containing cynaropicrin (Medium-Chain Triglyceride oil) with an aqueous phase of chitosan and salicin, followed by high-shear homogenization and sonication, and subsequently incorporated into a Carbopol gel. Five distinct formulations (F1-F5) were systematically developed and characterized for pH, viscosity, spreadability, particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), and morphology via TEM. Optimized nanoemulgels exhibited desirable particle sizes ranging from 81.63 ± 0.47 nm to 106.13 ± 0.75 nm, low PDI values (0.249 ± 0.002 to 0.337 ± 0.003), and strong negative zeta potentials (–25.2 ± 0.2 mV to –40.33 ± 0.21 mV), indicating good colloidal stability. Encapsulation efficiencies were notable, ranging from 80.94-91.80% for cynaropicrin and 64.52-81.40% for salicin. TEM analysis confirmed the presence of uniform, spherical nano-droplets. Crucially, in vitro release studies demonstrated a sustained release profile for both encapsulated drugs over a 24-hour period. These findings collectively suggest that the developed chitosan-based nanoemulgel system is a promising and effective platform for the co-delivery and controlled release of cynaropicrin and salicin.