SGLT2 Inhibitors and Curcumin Co-loaded Liposomal Formulations as Synergistic Delivery Systems for Heart Failure Therapy

<b>Background/Objectives</b>: As novel synergistic strategy for heart failure (HF), this study explores the formulation and characterization of liposomal systems co-loaded with SGLT2 inhibitors (dapagliflozin-DAPA and empagliflozin-EMPA) and curcumin (Cur). <b>Methods</b>: To enhance liposomal membrane stability and achieve sustained, controlled drug release, oleanolic acid (OA) was incorporated into the lipid bilayer, while the liposomal surface was coated with polyvinylpyrrolidone (PVP). <b>Results</b>: The resulting liposomes exhibited favorable physico-chemical properties (particle size ~170 nm, low PDI, negative zeta potential), high encapsulation efficiencies (up to 97%), and spherical morphology as confirmed by STEM. XRD and DSC analyses indicated successful API incorporation and amorphization within the lipid matrix, while PVP coating provided slight improvements in thermal stability. Trehalose proved to be an effective cryoprotectant, preserving liposome integrity after freeze-drying. In vitro release studies demonstrated sustained and delayed drug release, especially in PVP-coated and OA-containing formulations. <b>Conclusions</b>: All these findings highlight the promise of PVP-coated, OA-stabilized liposomal formulations co-loaded with SGLT2 inhibitors and Cur as biocompatible, multifunctional platforms for targeted HF therapy.