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Enhancing clomipramine antidepressive effect using nanocomplexes via different routes of administration: A
Abeer Salama1, Rabab Kamel2, Nourina N Ghoneim3
1Pharmacology Department, National Research Centre, El-Bohooth Street (P.O. 12622), Cairo, Egypt.
Iranian Journal of Basic Medical Sciences
|February 6, 2026
Summary
Intranasal clomipramine nano-complexes significantly boosted antidepressant effects in rats by reducing neurological toxicity. This novel nanoformulation offers a superior alternative to oral administration for depression treatment.
Area of Science:
- Pharmacology and Drug Delivery
- Neuroscience
- Materials Science
Background:
- Depression is a complex neurological disorder often treated with antidepressants like clomipramine.
- Current drug delivery methods face challenges in efficacy and side effects.
- Nanoformulations offer potential for enhanced drug delivery and therapeutic outcomes.
Purpose of the Study:
- To enhance the antidepressant effect of clomipramine using a novel nanoformulation.
- To investigate the efficacy of clomipramine nano-complexes administered via oral and intranasal routes.
- To evaluate the neuroprotective effects of the nanoformulation in a rat model of depression.
Main Methods:
- Depression was induced in Wistar albino rats using ciprofloxacin (CPX).
- Polyelectrolyte nanocomplexes (NC) of chitosan (CS) and gum arabic (GA) were prepared.
- Clomipramine HCl was loaded into NC and administered orally and intranasally, with comparisons to clomipramine solution and CPX.
Main Results:
- The optimal NC (CS:GA 1:1) exhibited small particle size and sustained release.
- Clomipramine-loaded NC treatment increased swimming time and levels of serotonin (5-HT), EAAT2, and GABA.
- NC treatment decreased malondialdehyde (MDA) and nitric oxide (NO) levels, showing neuroprotective effects.
Conclusions:
- Intranasal administration of clomipramine-loaded NC demonstrated superior antidepressant activity compared to the oral route.
- The nanoformulation effectively alleviated CPX-induced neurological toxicity.
- This study highlights the potential of intranasal nano-complexes for enhanced depression treatment.
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