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

Document Type : Original Article

Authors

1 Pharmacology Department, National Research Centre, El-Bohooth Street (P.O. 12622), Cairo, Egypt

2 Pharmaceutical Technology Department, National Research Centre, El-Bohooth Street, Cairo, Egypt

3 Egyptian Drug Authority, Cairo, Egypt

4 Department of Biochemistry, Faculty of Pharmacy, Heliopolis University,Cairo,Egypt

5 Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

10.22038/ijbms.2025.88730.19176

Abstract

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 50 mg/kg for 14 days to induce depression. Clomipramine HCl solution and the drug-loaded nano complexes (NC) were administrated for 14 days via the oral route (50 mg/kg) and intranasal route (500 µg/kg). 
Results: All the prepared drug-loaded nano-complexes (NC) were uniformly distributed (PDI ˂0.2), NC1 (composed of CS:GA 1:1) attained the smallest particle size (200.30 ± 26.07nm) and the most sustained release profile (Mean Release Time= 96.02± 8.36 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 (5-HT), excitatory amino acid transporter 2 (EAAT2) 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 5-HT and EAAT 2 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.

Keywords

Main Subjects

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Iranian Journal of Basic Medical Sciences
Volume 29, Issue 1
January 2026
Pages 55-64

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