Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution
Propranolol is the first-line drug for managing migraine attacks. D-limonene is a citrus oil known for its neuroprotective mechanism. Thus, the current work aims to design a thermo-responsive intranasal limonene-based microemulsion mucoadhesive nanogel to improve propranolol efficacy. Microemulsion...
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| Language: | English |
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MDPI AG
2023-06-01
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| Online Access: | https://www.mdpi.com/2310-2861/9/6/491 |
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| author | Kawthar K. Abla Souraya Domiati Rania El Majzoub Mohammed M. Mehanna |
| author_facet | Kawthar K. Abla Souraya Domiati Rania El Majzoub Mohammed M. Mehanna |
| author_sort | Kawthar K. Abla |
| collection | DOAJ |
| description | Propranolol is the first-line drug for managing migraine attacks. D-limonene is a citrus oil known for its neuroprotective mechanism. Thus, the current work aims to design a thermo-responsive intranasal limonene-based microemulsion mucoadhesive nanogel to improve propranolol efficacy. Microemulsion was fabricated using limonene and Gelucire<sup>®</sup> as the oily phase, Labrasol<sup>®</sup>, Labrafil<sup>®</sup>, and deionized water as the aqueous phase, and was characterized regarding its physicochemical features. The microemulsion was loaded in thermo-responsive nanogel and evaluated regarding its physical and chemical properties, in vitro release, and ex vivo permeability through sheep nasal tissues. Its safety profile was assessed via histopathological examination, and its capability to deliver propranolol effectively to rats’ brains was examined using brain biodistribution analysis. Limonene-based microemulsion was of 133.7 ± 0.513 nm diametric size with unimodal size distribution and spheroidal shape. The nanogel showed ideal characteristics with good mucoadhesive properties and in vitro controlled release with 1.43-fold enhancement in ex vivo nasal permeability compared with the control gel. Furthermore, it displayed a safe profile as elucidated by the nasal histopathological features. The nanogel was able to improve propranolol brain availability with C<sub>max</sub> 970.3 ± 43.94 ng/g significantly higher than the control group (277.7 ± 29.71 ng/g) and with 382.4 % relative central availability, which confirms its potential for migraine management. |
| first_indexed | 2024-03-11T02:26:43Z |
| format | Article |
| id | doaj.art-c672b7c2e978495c8bbd2441a4b32e1e |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-11T02:26:43Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj.art-c672b7c2e978495c8bbd2441a4b32e1e2023-11-18T10:32:41ZengMDPI AGGels2310-28612023-06-019649110.3390/gels9060491Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain BiodistributionKawthar K. Abla0Souraya Domiati1Rania El Majzoub2Mohammed M. Mehanna3Pharmaceutical Nanotechnology Research Lab, Faculty of Pharmacy, Beirut Arab University, Beirut P.O. Box 11-5020, LebanonDepartment of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut P.O. Box 11-5020, LebanonDepartment of Biomedical Sciences, Faculty of Pharmacy, Lebanese International University, Beirut P.O. Box 11-5020, LebanonDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptPropranolol is the first-line drug for managing migraine attacks. D-limonene is a citrus oil known for its neuroprotective mechanism. Thus, the current work aims to design a thermo-responsive intranasal limonene-based microemulsion mucoadhesive nanogel to improve propranolol efficacy. Microemulsion was fabricated using limonene and Gelucire<sup>®</sup> as the oily phase, Labrasol<sup>®</sup>, Labrafil<sup>®</sup>, and deionized water as the aqueous phase, and was characterized regarding its physicochemical features. The microemulsion was loaded in thermo-responsive nanogel and evaluated regarding its physical and chemical properties, in vitro release, and ex vivo permeability through sheep nasal tissues. Its safety profile was assessed via histopathological examination, and its capability to deliver propranolol effectively to rats’ brains was examined using brain biodistribution analysis. Limonene-based microemulsion was of 133.7 ± 0.513 nm diametric size with unimodal size distribution and spheroidal shape. The nanogel showed ideal characteristics with good mucoadhesive properties and in vitro controlled release with 1.43-fold enhancement in ex vivo nasal permeability compared with the control gel. Furthermore, it displayed a safe profile as elucidated by the nasal histopathological features. The nanogel was able to improve propranolol brain availability with C<sub>max</sub> 970.3 ± 43.94 ng/g significantly higher than the control group (277.7 ± 29.71 ng/g) and with 382.4 % relative central availability, which confirms its potential for migraine management.https://www.mdpi.com/2310-2861/9/6/491brain distributionBBBlimonenemicroemulsionthermo-sensitivemucoadhesion |
| spellingShingle | Kawthar K. Abla Souraya Domiati Rania El Majzoub Mohammed M. Mehanna Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution Gels brain distribution BBB limonene microemulsion thermo-sensitive mucoadhesion |
| title | Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution |
| title_full | Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution |
| title_fullStr | Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution |
| title_full_unstemmed | Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution |
| title_short | Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution |
| title_sort | propranolol loaded limonene based microemulsion thermo responsive mucoadhesive nasal nanogel design in vitro assessment ex vivo permeation and brain biodistribution |
| topic | brain distribution BBB limonene microemulsion thermo-sensitive mucoadhesion |
| url | https://www.mdpi.com/2310-2861/9/6/491 |
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