Development and characterization of selegiline loaded liquid crystalline nanoparticle based intranasal gel for targeted brain delivery

Parkinson’s disease (PD) is a progressive neurodegenerative illness linked to oxidative stress, mitochondrial dysfunction, dopaminergic neuronal loss, and compromised neurotransmitter signalling. Selective MAO-B inhibitors such as selegiline hydrochloride (SH) are often used to treat PD symptoms by lowering dopamine breakdown. However, considerable first-pass metabolism, variable oral bioavailability, and blood–brain barrier (BBB) limit its clinical efficacy, leading to decreased therapeutic efficacy. Thus, the current research was aimed to design an intranasal gel, with liquid crystalline nanoparticles (LCN) as carrier for targeted selegiline delivery to enhance brain targeting and treatment efficiency in PD. The stable, optimized SH-LCN formulation with nanoscale particle size and high drug encapsulation was further incorporated into a gellan gum-based system to promote nasal residence with sustained release. Structural studies confirmed the successful drug inclusion in an amorphous form within an organized lipid nanostructure. Long-term nasal retention was reinforced by the formulation’s mucoadhesive strength and sustained drug release. In-vivo studies have shown significantly improved brain delivery and reduced systemic exposure after intranasal administration compared to intravenous drug solutions, indicating efficient transport from the nose to the brain (NTB). Improved pharmacodynamics parameters, such as restoration of dopamine levels, diminished oxidative stress and inflammatory responses, suggested maximized neuroprotective effects. Additionally, it was discovered that the medication is safe and does not cause nasal mucosal irritation. Overall, the LCN platform proved to be a non-invasive and efficient way to boost the transport of SH to the brain, which could lead to better treatment outcomes for PD cases. Intranasal, selegiline LCN gel enhanced brain-targeted delivery. In-situ gel improved nasal retention and drug release. LCN showed higher drug loading with stable, nanosized particles. Intranasal delivery reduced systemic exposure and improved brain delivery. Formulation restored dopamine and reduced oxidative stress in Parkinson’s disease.