Development and Optimization of an Eplerenone-Loaded Liposomal In Situ Gel for Enhanced Intranasal Delivery

Objectives: this study aimed to develop and optimize an intranasal delivery system for Eplerenone (EPL) by incorporating Eplerenone-loaded liposomes (Elip) into an in situ gel system (Elip-GG). The goal was to prolong the residence time of the drug in the nasal cavity and ensure sustained release. Methods: Elip and unloaded liposomes were prepared using the thin-film hydration method. Key formulation variables such as encapsulation efficiency (EE%), mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were optimized. The Elip was then incorporated into a gellan gum (GG) in situ gel to form Elip-GG. The Elip-GG formulation was evaluated based on parameters such as pH, viscosity, rheological behavior, mechanical properties, and in vitro release. Results: the optimal Elip formulation exhibited an EE of 86.3%, a mean particle size of 86.56 nm, a PDI of 0.29, and a ZP of -29.86 mV. The cumulative drug release from the Elip-GG formulation exceeded 93% after 2.5 h. The Elip-GG formulation significantly increased the sustained release of Eplerenone when administered intranasally, offering a promising alternative to oral and parenteral delivery methods for hydrophilic antihypertensive drugs.