Niosomal Bupropion: Exploring Therapeutic Frontiers through Behavioral Profiling.

Area of Science:

• Neuroscience
• Pharmacology
• Materials Science

Background:

• Bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), is FDA-approved for major depressive disorder (MDD).
• Bupropion's use can lead to adverse effects like seizures and liver failure, necessitating safer delivery methods.
• Niosomal drug delivery systems offer potential for improved therapeutic efficacy and reduced toxicity.

Purpose of the Study:

• To nanoformulate bupropion (Bup) into niosomal vesicles to enhance its efficacy and reduce required doses.
• To optimize the niosomal formulation for stability, sustained release, and minimal toxicity.
• To evaluate the in vivo efficacy of the optimized bupropion-loaded niosomes in a zebrafish model of depression.

Main Methods:

• Bupropion-loaded niosomes were synthesized using a thin film hydration method with sorbitan esters (Span 20, 40, 60) and cholesterol.
• Niosomal formulations were optimized based on stability and drug entrapment, with a focus on the cholesterol-to-surfactant ratio.
• In vitro and in vivo toxicity, drug release kinetics in artificial cerebrospinal fluid (ACSF), and behavioral effects in a reserpine-induced zebrafish depression model were assessed.

Main Results:

• The optimal niosome formulation (Bup@N20C) utilized Span 20 and a cholesterol-to-surfactant ratio of 1:1.5, exhibiting high stability.
• Bup@N20C demonstrated sustained bupropion release in ACSF and showed minimal in vitro and in vivo toxicity.
• In the zebrafish model, Bup@N20C significantly increased exploration activity and reduced depression-like behaviors, outperforming the positive control.

Conclusions:

• Niosomal formulation of bupropion (Bup@N20C) is a promising strategy for delivering the drug to the brain, potentially bypassing the blood-brain barrier.
• This nanoformulation offers improved efficacy and reduced toxicity compared to conventional bupropion administration.
• Bup@N20C holds potential for more effective and safer treatment of major depressive disorder by improving mood and reducing depressive behaviors.