Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality
Ischemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranas...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2104405 |
| _version_ | 1811312727825580032 |
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| author | Eman A. Bseiso Sarah A. AbdEl-Aal Maha Nasr Omaima A. Sammour Nabaweya A. Abd El Gawad |
| author_facet | Eman A. Bseiso Sarah A. AbdEl-Aal Maha Nasr Omaima A. Sammour Nabaweya A. Abd El Gawad |
| author_sort | Eman A. Bseiso |
| collection | DOAJ |
| description | Ischemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranasal route) became a popular approach. In the current study, melatonin (MEL) was loaded in lipidic nanocapsules (LNCs) prepared using the phase inversion method, and characterized in terms of size, polydispersity, zeta potential, in vitro drug release, viscosity, storage stability, and ex vivo permeation across sheep nasal mucosa. Moreover, MEL-LNCs were tested for efficacy in cerebral ischemia/reperfusion (I/R/) injury model through histopathological assessment, and analysis of oxidative stress markers, pro-inflammatory cytokines, and apoptotic markers. Results showed that LNCs exhibited particle size ranging from 18.26 to 109.8 nm, negative zeta potential, good storage stability, spherical morphology, and a burst release followed by a sustained release pattern. LNCs exhibited 10.35 folds higher permeation of MEL than the drug solution across sheep nasal mucosa. Post-ischemic intranasal administration of MEL-LNCs revealed lowering of oxidative stress manifested by a decrease in malondialdehyde levels, and elevation of glutathione and superoxide dismutase levels, lowering of the inflammatory markers tumor necrosis factor-α, NO, myeloperoxidase, and significant inhibition of Caspase-3 activity as an apoptotic marker. Western blot analysis delineated a recovery of protein expression Nrf-2 and HO-1 with downregulation in the parent inflammatory markers nuclear factor kappa B p65, inducible nitric oxide synthase, Bax, and Cytochrome C expressions, and upregulation of B-cell lymphoma-2 Bcl-2, hence promoting neuronal survival. This was supported by histological evidence, revealing significant restoration of hippocampal neurons. In light of the above, it can be concluded that MEL-LNCs could be a promising delivery system for nose to brain delivery for treatment of cerebral ischemia. |
| first_indexed | 2024-04-13T10:41:39Z |
| format | Article |
| id | doaj.art-acf1a09782f44e0ea0db3a56d912be44 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-13T10:41:39Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-acf1a09782f44e0ea0db3a56d912be442022-12-22T02:49:55ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012912469248010.1080/10717544.2022.2104405Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modalityEman A. Bseiso0Sarah A. AbdEl-Aal1Maha Nasr2Omaima A. Sammour3Nabaweya A. Abd El Gawad4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza Governorate, EgyptPharmacology and Toxicology Division, Department of Pharmacy, KUT University College, Al Kut, Wasit52001, IraqDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain-Shams University, Cairo, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain-Shams University, Cairo, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza Governorate, EgyptIschemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranasal route) became a popular approach. In the current study, melatonin (MEL) was loaded in lipidic nanocapsules (LNCs) prepared using the phase inversion method, and characterized in terms of size, polydispersity, zeta potential, in vitro drug release, viscosity, storage stability, and ex vivo permeation across sheep nasal mucosa. Moreover, MEL-LNCs were tested for efficacy in cerebral ischemia/reperfusion (I/R/) injury model through histopathological assessment, and analysis of oxidative stress markers, pro-inflammatory cytokines, and apoptotic markers. Results showed that LNCs exhibited particle size ranging from 18.26 to 109.8 nm, negative zeta potential, good storage stability, spherical morphology, and a burst release followed by a sustained release pattern. LNCs exhibited 10.35 folds higher permeation of MEL than the drug solution across sheep nasal mucosa. Post-ischemic intranasal administration of MEL-LNCs revealed lowering of oxidative stress manifested by a decrease in malondialdehyde levels, and elevation of glutathione and superoxide dismutase levels, lowering of the inflammatory markers tumor necrosis factor-α, NO, myeloperoxidase, and significant inhibition of Caspase-3 activity as an apoptotic marker. Western blot analysis delineated a recovery of protein expression Nrf-2 and HO-1 with downregulation in the parent inflammatory markers nuclear factor kappa B p65, inducible nitric oxide synthase, Bax, and Cytochrome C expressions, and upregulation of B-cell lymphoma-2 Bcl-2, hence promoting neuronal survival. This was supported by histological evidence, revealing significant restoration of hippocampal neurons. In light of the above, it can be concluded that MEL-LNCs could be a promising delivery system for nose to brain delivery for treatment of cerebral ischemia.https://www.tandfonline.com/doi/10.1080/10717544.2022.2104405Lipid nanocapsulesmelatoninnose to brain deliverystrokebrain ischemia |
| spellingShingle | Eman A. Bseiso Sarah A. AbdEl-Aal Maha Nasr Omaima A. Sammour Nabaweya A. Abd El Gawad Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality Drug Delivery Lipid nanocapsules melatonin nose to brain delivery stroke brain ischemia |
| title | Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality |
| title_full | Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality |
| title_fullStr | Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality |
| title_full_unstemmed | Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality |
| title_short | Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality |
| title_sort | nose to brain delivery of melatonin lipidic nanocapsules as a promising post ischemic neuroprotective therapeutic modality |
| topic | Lipid nanocapsules melatonin nose to brain delivery stroke brain ischemia |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2104405 |
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