Syringic Acid–Loaded Emulsomes as a Neuroprotective Delivery System: Formulation Optimization and In‑Vivo Pharmacokinetic Evaluation

Abstract

Syringic acid (SA) demonstrates significant anti-inflammatory, antioxidant, and neuroprotective properties. Unfortunately, its clinical applicability is limited by low solubility and low bioavailability. SA-loaded emulsomes were developed to overcome these limitations. The emulsomes were prepared using thin-film hydration method and optimized by a Central Composite Design. Three independent variables were studied: the solid lipid-to-phosphatidylcholine ratio, drug amount, and solid lipid type (trilaurin or tripalmitin). The measured responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimized formula exhibited an EE% of 61.92 ± 0.09%, a PS of 190.02 ± 0.13 nm, a PDI of 0.21 ± 0.07 and a ZP of -36.3 ± 0.98 mV. In-vitro release studies demonstrated a sustained release profile, with 92% of SA released over 24 h. The relative bioavailability of SA from the optimized formula was 219% compared to the unformulated drug. A physiologically based pharmacokinetic (PBPK) model was developed to predict plasma and tissue distribution. The model predicted a twofold increase in brain bioavailability, suggesting the potential for improved brain penetration and retention. These findings establish emulsomes as a promising nanoplatform for overcoming syringic acid's biopharmaceutical barriers and advancing its clinical potential.