Development of Nanoemulsion-Based In-Situ Gel Formulation of Escitalopram Oxalate for Intranasal Delivery in Depression Therapy

This study developed a nanoemulsion-based in-situ gel for intranasal delivery of Escitalopram Oxalate to enhance its bioavailability and antidepressant efficacy. The nanoemulsion was prepared via high-energy emulsification using Arachis oil: Caproyl 90 (1:1), Tween 80, and PEG 400 as oil, surfactant, and cosurfactant. Formulations optimized by Central Composite Design were evaluated for droplet size, polydispersity index (PDI), zeta potential, and drug encapsulation efficiency. Selected nanoemulsions were incorporated into a thermosensitive poloxamer 407 gel.The in-situ gel showed a gelation temperature of 34 ± 1°C, suitable viscosity, pH 6.4 ± 0.93, and 97% drug content. The nanoemulsion had a mean droplet size of 34.93 nm, PDI 0.1955, and zeta potential − 17 mV. In vitro release studies demonstrated controlled Escitalopram release over 8 hours. Ex vivo permeation through nasal mucosa was significantly higher for the gel compared to the nanoemulsion alone. Nasal ciliary toxicity and RPMI 2650 cell line studies confirmed formulation safety. Pharmacodynamic tests in Wistar rats revealed that the nanoemulsion and in-situ gel markedly reduced depressive-like behaviors compared to oral Escitalopram solution.In conclusion, the optimized intranasal formulation improved drug bioavailability, sustained release, antidepressant efficacy, and safety, offering a promising non-invasive alternative for depression treatment by directly targeting the CNS.