Simulation of nanocarrier-based targeted delivery of an antidepressant for major depressive disorder

ABSTRACTAlthough Depression or Major Depressive Disorder (MDD) affects nearly 15% of the adult population, yet, common antidepressants that work through the monoamine hypothesis of depression are not effective against all types of MDD. The other hypothesis, blocking N-methyl D-aspartate (NMDA) receptors (NMDAR) with antagonists to promote antidepressant effects, is not very useful because of the adverse side effects of the NMDA antagonists. In this study, we have proposed a method involving the specific drug delivery of an antidepressant, using nanocarriers. The introduction of nanocarrier encapsulated potent NMDAR antagonist, R-ketamine, in the target neuronal environments of varying membrane potentials of the central nervous system was studied using in-silico coarse grain simulation of hollow spherical polypyrrole nanocarriers or increasing size. The membrane potential ruptures the nanocarrier and releases the drug R-ketamine, which has a high-binding affinity for NMDAR. Such coarse grain simulations are an interesting and emerging field of study and shed preliminary light on the theoretical behaviour of nanopharmaceuticals in vivo. The results of these in silico findings need to be validated with in vivo experimentation to develop an improved antidepressant delivery nanoformulation.KEYWORDS: DepressionMajor depressive disorder‌nanocarriermolecular dynamicsantidepressant drug delivery AcknowledgementsThe authors would like to thank Prof. Shrikant Kukreti, Department of Chemistry, University of Delhi for his valuable discussions.Disclosure statementNo potential conflict of interest was reported by the author(s).