Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model

Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER’s antidepressant activity, a QER-loaded transferosome (...

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Main Authors: Mohammed H. Elkomy, Fatma I. Abo El-Ela, Randa Mohammed Zaki, Omar A. Alsaidan, Mohammed Elmowafy, Ameeduzzafar Zafar, Khaled Shalaby, Mohamed A. Abdelgawad, Hany A. Omar, Rania Salama, Hussein M. Eid
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/8/2095
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author Mohammed H. Elkomy
Fatma I. Abo El-Ela
Randa Mohammed Zaki
Omar A. Alsaidan
Mohammed Elmowafy
Ameeduzzafar Zafar
Khaled Shalaby
Mohamed A. Abdelgawad
Hany A. Omar
Rania Salama
Hussein M. Eid
author_facet Mohammed H. Elkomy
Fatma I. Abo El-Ela
Randa Mohammed Zaki
Omar A. Alsaidan
Mohammed Elmowafy
Ameeduzzafar Zafar
Khaled Shalaby
Mohamed A. Abdelgawad
Hany A. Omar
Rania Salama
Hussein M. Eid
author_sort Mohammed H. Elkomy
collection DOAJ
description Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER’s antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.
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spelling doaj.art-a4d5c625e62942779049c7c73f7187e32023-11-19T02:36:44ZengMDPI AGPharmaceutics1999-49232023-08-01158209510.3390/pharmaceutics15082095Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal ModelMohammed H. Elkomy0Fatma I. Abo El-Ela1Randa Mohammed Zaki2Omar A. Alsaidan3Mohammed Elmowafy4Ameeduzzafar Zafar5Khaled Shalaby6Mohamed A. Abdelgawad7Hany A. Omar8Rania Salama9Hussein M. Eid10Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaCollege of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, AustraliaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, EgyptDepression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER’s antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.https://www.mdpi.com/1999-4923/15/8/2095intranasaldepressionpharmacodynamicsquercetinforced swim testtransferosomes
spellingShingle Mohammed H. Elkomy
Fatma I. Abo El-Ela
Randa Mohammed Zaki
Omar A. Alsaidan
Mohammed Elmowafy
Ameeduzzafar Zafar
Khaled Shalaby
Mohamed A. Abdelgawad
Hany A. Omar
Rania Salama
Hussein M. Eid
Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
Pharmaceutics
intranasal
depression
pharmacodynamics
quercetin
forced swim test
transferosomes
title Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
title_full Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
title_fullStr Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
title_full_unstemmed Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
title_short Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model
title_sort intranasal nanotransferosomal gel for quercetin brain targeting ii antidepressant effect in an experimental animal model
topic intranasal
depression
pharmacodynamics
quercetin
forced swim test
transferosomes
url https://www.mdpi.com/1999-4923/15/8/2095
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