Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain
Chitosan-based polymeric micelles are promising non-viral nanocarriers for safe and targeted gene delivery. Multi-functionalized chitosan polymeric micelles were prepared by grafting fatty acid, cell-penetrating peptide, and mannose on the chitosan backbone. The polymeric micelles were subjected to...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/13019 |
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| author | Avinash Gothwal Richard Nii Lante Lamptey Riddhi Trivedi Bivek Chaulagain Jagdish Singh |
| author_facet | Avinash Gothwal Richard Nii Lante Lamptey Riddhi Trivedi Bivek Chaulagain Jagdish Singh |
| author_sort | Avinash Gothwal |
| collection | DOAJ |
| description | Chitosan-based polymeric micelles are promising non-viral nanocarriers for safe and targeted gene delivery. Multi-functionalized chitosan polymeric micelles were prepared by grafting fatty acid, cell-penetrating peptide, and mannose on the chitosan backbone. The polymeric micelles were subjected to surface morphology and surface topography using scanning electron microscopy and atomic force microscopy, respectively. The hemotoxic profile of the prepared polymeric micelles was established against erythrocytes and was found to be <5% hemotoxic up to the concentration of 600 µg/mL. In vitro <i>ApoE2</i> expression in primary astrocytes and neurons was analyzed. Multi-functionalized polymeric micelles produced greater (<i>p</i> < 0.05) transfection in astrocytes and neurons in comparison to mono-functionalized micelles. Intranasal administration of polymeric micelles/<i>pApoE2</i> polyplex led to significantly higher (<i>p</i> < 0.05) in vivo <i>pApoE2</i> expression than chitosan and unfunctionalized polymeric micelles-treated mice groups. The outcomes of this study predict that the developed multi-functionalized polymeric micelles could be an effective and safe gene delivery platform to the brain through the intranasal route. |
| first_indexed | 2024-03-10T23:51:45Z |
| format | Article |
| id | doaj.art-b8032bc75ae245c19890862909089fd1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:51:45Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b8032bc75ae245c19890862909089fd12023-11-19T01:34:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161301910.3390/ijms241613019Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice BrainAvinash Gothwal0Richard Nii Lante Lamptey1Riddhi Trivedi2Bivek Chaulagain3Jagdish Singh4Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USADepartment of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USADepartment of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USADepartment of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USADepartment of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USAChitosan-based polymeric micelles are promising non-viral nanocarriers for safe and targeted gene delivery. Multi-functionalized chitosan polymeric micelles were prepared by grafting fatty acid, cell-penetrating peptide, and mannose on the chitosan backbone. The polymeric micelles were subjected to surface morphology and surface topography using scanning electron microscopy and atomic force microscopy, respectively. The hemotoxic profile of the prepared polymeric micelles was established against erythrocytes and was found to be <5% hemotoxic up to the concentration of 600 µg/mL. In vitro <i>ApoE2</i> expression in primary astrocytes and neurons was analyzed. Multi-functionalized polymeric micelles produced greater (<i>p</i> < 0.05) transfection in astrocytes and neurons in comparison to mono-functionalized micelles. Intranasal administration of polymeric micelles/<i>pApoE2</i> polyplex led to significantly higher (<i>p</i> < 0.05) in vivo <i>pApoE2</i> expression than chitosan and unfunctionalized polymeric micelles-treated mice groups. The outcomes of this study predict that the developed multi-functionalized polymeric micelles could be an effective and safe gene delivery platform to the brain through the intranasal route.https://www.mdpi.com/1422-0067/24/16/13019intranasalmulti-functionalized chitosan micellesgene deliverybrain targetingpolyplex |
| spellingShingle | Avinash Gothwal Richard Nii Lante Lamptey Riddhi Trivedi Bivek Chaulagain Jagdish Singh Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain International Journal of Molecular Sciences intranasal multi-functionalized chitosan micelles gene delivery brain targeting polyplex |
| title | Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain |
| title_full | Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain |
| title_fullStr | Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain |
| title_full_unstemmed | Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain |
| title_short | Non-Invasive Intranasal Delivery of <i>pApoE2</i>: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain |
| title_sort | non invasive intranasal delivery of i papoe2 i effect of multiple dosing on the apoe2 expression in mice brain |
| topic | intranasal multi-functionalized chitosan micelles gene delivery brain targeting polyplex |
| url | https://www.mdpi.com/1422-0067/24/16/13019 |
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