Enhanced behavioral impact of optimized bupropion-encapsulated bilosomes over traditional niosomes treating depression.

Abstract

Bupropion (Bpn), an FDA-approved NDRI (norepinephrine-dopamine reuptake inhibitor), poses risks of seizures and liver failure due to its stimulant properties, necessitating the development of alternative formulations. This research aims to develop a Bpn nanoformulation within bilosomal vesicles to enhance therapeutic efficacy at lower doses, using three bile salts, span 20 surfactants, and cholesterol via thin-film hydration. Optimization of bilosomal stability is achieved by trialing various ingredient concentrations, identifying a surfactant-to-cholesterol-to-bile salt ratio of 1.5:1:0.17 µM, with sodium cholate (B.SC_F) yielding the most stable system. Bpn encapsulated in the optimized bilosomal vesicle (Bpn@B.SC _F) demonstrated high encapsulation efficiency of 78.142 ± 11.07% and drug-retaining capacity compared to the niosomal system. The in vitro and in vivo toxicity profile of the product is superior to the niosomal system and shows negligible toxicity with a viability rate of not less than 95%, with a sustained release profile in artificial cerebrospinal fluid (ACSF). In vivo, behavioral analysis on zebrafish revealed that Bpn@B.SC _F treatment more effectively improved depressive behavior compared to free Bpn and other treatments, evidenced by increased exploration rates and reduced irregular movements, as shown through statistical and trajectory data. Hence, it is concluded that the bilosomal structure, compared to the niosomal system, is a better carrier of drugs to achieve brain delivery and improve mood.