Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies
<b>Background/Objectives</b>: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repea...
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2025-01-01
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| author | Amani M. El Sisi Essam M. Eissa Ahmed H. E. Hassan Marina A. Bekhet Fatma I. Abo El-Ela Eun Joo Roh Rasha M. Kharshoum Adel A. Ali |
| author_facet | Amani M. El Sisi Essam M. Eissa Ahmed H. E. Hassan Marina A. Bekhet Fatma I. Abo El-Ela Eun Joo Roh Rasha M. Kharshoum Adel A. Ali |
| author_sort | Amani M. El Sisi |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. <b>Methods</b>: Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. <b>Results</b>: The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm<sup>2</sup>. Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension (<i>p</i> < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics’ and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. <b>Conclusions</b>: CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-fbb8db48e7204da794f4e242104a1c622025-01-24T13:45:09ZengMDPI AGPharmaceuticals1424-82472025-01-011814610.3390/ph18010046Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal StudiesAmani M. El Sisi0Essam M. Eissa1Ahmed H. E. Hassan2Marina A. Bekhet3Fatma I. Abo El-Ela4Eun Joo Roh5Rasha M. Kharshoum6Adel A. Ali7Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, EgyptChemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt<b>Background/Objectives</b>: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. <b>Methods</b>: Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. <b>Results</b>: The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm<sup>2</sup>. Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension (<i>p</i> < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics’ and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. <b>Conclusions</b>: CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant.https://www.mdpi.com/1424-8247/18/1/46mirtazapinedepressioncationic leciplexesnose-to-brain targetingin vivo studypharmacodynamics |
| spellingShingle | Amani M. El Sisi Essam M. Eissa Ahmed H. E. Hassan Marina A. Bekhet Fatma I. Abo El-Ela Eun Joo Roh Rasha M. Kharshoum Adel A. Ali Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies Pharmaceuticals mirtazapine depression cationic leciplexes nose-to-brain targeting in vivo study pharmacodynamics |
| title | Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies |
| title_full | Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies |
| title_fullStr | Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies |
| title_full_unstemmed | Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies |
| title_short | Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies |
| title_sort | nose to brain delivery of chitosan grafted leciplexes for promoting the bioavailability and antidepressant efficacy of mirtazapine in vitro assessment and animal studies |
| topic | mirtazapine depression cationic leciplexes nose-to-brain targeting in vivo study pharmacodynamics |
| url | https://www.mdpi.com/1424-8247/18/1/46 |
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