Investigation on Nanoformulated Antidepressants against major depressive disorders

Abstract

ABSTRACT newlineThis thesis explored the engineering of nanovesicular structures to encapsulate antidepressants to improve therapeutic efficacy. The research aims to optimize the levels of nonionic surfactants and cholesterol for the development of niosomal vesicles, using bupropion both as a spectroscopic probe and as an antidepressant. The optimal formulation was achieved with 1.5 and#956;M of Span 20/40/60 surfactants and 1 µM cholesterol, resulting in niosomal vesicles with an entrapment efficiency of approximately 29.1%, 33.1%, and 49%, respectively. The biocompatibility of niosomal vesicles containing bupropion was assessed in vitro using V79 and PC12 cell lines and in vivo using zebrafish embryos. The enhanced efficacy was demonstrated through improved behavioral assessments in stress-induced adult zebrafish. An additional optimization involved incorporating 0.17 µM sodium cholate (SC), sodium deoxycholate (SDC), and sodium taurocholate (STC) bile salts into the standard niosomal formulation in the form of bilosomes, which increased the entrapment efficiency to 92.6%, 90.1%, and 91.1% respectively, with enhancement in therapeutic efficacy while minimizing toxicity. The formulation s stability at refrigerated temperatures and its superior release profile in artificial cerebrospinal fluid, compared to a buffer with biological pH, highlight its potential as an effective antidepressant carrier, offering improved therapeutic efficacy. With the optimized bilosomal vesicles, SSRIs drugs Sertraline and Citalopram were loaded and characterized. The results demonstrated that the optimal bilosomal nanoformulation reduced the toxicity profile both in vitro and in vivo when compared with the pure form of the drug. The release of drug from the vesicle was shown to be sustained in ACSF medium provided with high drug retaining capacity and high vesicle stability. The provided advantageous characteristics can potentially improve the therapeutic efficacy of the drug. newline newline