Vilazodone Hydrochloride-Loaded Nanostructured Lipid Carrier In Situ Gel for Intranasal Nose-to-Brain Antidepressant Delivery

Abstract

The Oral delivery of vilazodone hydrochloride (VLZ), a serotonin partial agonist–reuptake inhibitor for major depressive disorder, suffers from extensive hepatic first-pass metabolism, food-dependent absorption, and poor blood–brain barrier (BBB) penetration, limiting its central therapeutic impact. Here, VLZ-loaded nanostructured lipid carriers (NLCs) were engineered and embedded within a Poloxamer 407/188–chitosan thermosensitive in situ gel to enable direct nose-to-brain delivery. The NLCs were fabricated by combined high-shear and high-pressure homogenisation and optimised through central composite design, yielding a batch with particle size 24.74 ± 2.23 nm, polydispersity index 0.248 ± 0.012, and entrapment efficiency 91.37 ± 4.56%. The lyophilised NLCs were incorporated into an in situ gel with a physiologically appropriate gelation temperature of 34°C and gelation time of 42 s. Fourier Transform Infrared FTIR spectroscopy confirmed complete drug encapsulation, evidenced by disappearance of the diagnostic nitrile (C≡N) absorption band, while DSC and XRPD verified conversion of VLZ to an amorphous state within the lipid matrix. Drug release followed Korsmeyer–Peppas kinetics, sustained over 24 h, and the formulation remained stable under refrigerated storage. In Swiss albino mice, the intranasal NLC-in situ gel (1 mg/kg) produced a profound antidepressant-like effect relative to oral pure drug (10 mg/kg) across open field, tail suspension, and sucrose preference tests, consistent with enhanced nose-to-brain delivery via the olfactory and trigeminal pathways. Hence this nanocarrier–hydrogel strategy offers a promising, non-invasive route to enhanced CNS delivery of antidepressants.