Development and Validation of RP-HPLC Method for <i>trans</i> -Resveratrol in HPβCD-Loaded Stealth Liposomes: Stability and Release Studies

<i>trans</i>-Resveratrol (<i>trans</i>-RES) and <i>cis</i>-resveratrol are isomers that are difficult to separate due to their structural similarities. This study developed a method to enhance the solubility and stability of <i>trans</i>-RES, focusing on preventing its isomerization to the inactive <i>cis</i> form. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was optimized for quantifying <i>trans</i>-RES complexed with hydroxypropyl-β-cyclodextrin (HPβCD) in stealth liposomes. The technique used an isocratic mobile phase of water:acetonitrile (65:35 v/v) at a flow rate of 1 mL/min, with UV detection at 306 nm. Validation showed excellent linearity (<i>R</i> ² = 0.9997), precision (RSD < 2%), accuracy (98-102% recovery), and sensitivity (LOD 0.96 μg/mL, LOQ 2.91 μg/mL), with high resolution (<i>R</i> _s > 16.5) between <i>trans</i>- and <i>cis</i>-isomers and robustness against minor parameter variations. The dual-delivery system combined HPβCD inclusion complexes with stealth liposomes. Liposomal formulations F1-F5 showed sustained <i>trans</i>-RES release over 24 h, with F5 complexed in HPβCD demonstrating the sustained release profile (49.8% at 12 h). Release kinetics followed the Korsmeyer-Peppas model (<i>R</i> ² > 0.90), indicating a non-Fickian mechanism. Furthermore, the formulation protected <i>trans</i>-RES from UV-induced isomerization, confirming enhanced stability.