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

## TL;DR

This study shows that using nanocomplexes to deliver clomipramine through the nose improves its antidepressant effect compared to oral delivery in a rat model.

## Contribution

The novel contribution is demonstrating enhanced antidepressant activity of clomipramine via intranasal nanocomplex delivery over oral administration.

## Key findings

- Clomipramine-loaded nanocomplexes via intranasal route showed higher antidepressant activity than oral administration.
- Intranasal delivery restored brain serotonin and EAAT2 levels to normal and reduced oxidative stress markers.
- Nanocomplexes with a 1:1 chitosan:gum arabic ratio had optimal particle size and sustained drug release.

## Abstract

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).

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).

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.

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.