Enhancing clomipramine antidepressive effect using nanocomplexes via different routes of administration: A comparative study

Objective(s): Enhancing clomipramine anti-depressive effect using a nanoformulation and investigating its effect via different routes of administration (oral and intranasal) in a depression rat model. Polyelectrolytes nanocomplexes (NC) were prepared by an all-aqueous technique and were composed of different ratios of chitosan (CS) and gum arabic (GA). Materials and Methods: Ciprofloxacin (CPX) was administered orally to adult male Wistar albino rats at a dose of ۵۰ mg/kg for ۱۴ days to induce depression. Clomipramine HCl solution and the drug-loaded nano complexes (NC) were administrated for ۱۴ days via the oral route (۵۰ mg/kg) and intranasal route (۵۰۰ µg/kg). Results: All the prepared drug-loaded nano-complexes (NC) were uniformly distributed (PDI ˂۰.۲), NC۱ (composed of CS:GA ۱:۱) attained the smallest particle size (۲۰۰.۳۰ ± ۲۶.۰۷nm) and the most sustained release profile (Mean Release Time= ۹۶.۰۲± ۸.۳۶ min.) and has a spherical outline as detected by transmission electron microscope. Treatment with clomipramine-loaded NC via oral and intranasal routes elevated swimming time, serotonin (۵-HT), excitatory amino acid transporter ۲ (EAAT۲) and Gamma-aminobutyric acid (GABA) brain contents, decreased brain content of malondialdehyde (MDA) and nitric oxide (NO), and ameliorated nuclear pyknosis and degeneration of neurons compared to CPX and clomipramine solution. Clomipramine-loaded NC via intranasal routes returned the brain content of ۵-HT and EAAT ۲ to its normal level and has effect superior than oral route.Conclusion: Clomipramine-loaded NC administered via intranasal route showed an enhanced effect and a higher antidepressant activity than the traditional oral route through alleviating CPX neurological toxicity.

کلیدواژه ها:

Depression ، Ciprofloxacin ، clomipramine ، nanocomplex ، chitosan ، gum arabic ، GAPA/EAAT۲