Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis
Purpose: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral ad...
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| Format: | Article |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/4047 |
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| author | Ehtesham Shamsher Reas S. Khan Benjamin M. Davis Kimberly Dine Vy Luong M. Francesca Cordeiro Kenneth S. Shindler |
| author_facet | Ehtesham Shamsher Reas S. Khan Benjamin M. Davis Kimberly Dine Vy Luong M. Francesca Cordeiro Kenneth S. Shindler |
| author_sort | Ehtesham Shamsher |
| collection | DOAJ |
| description | Purpose: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral administration of resveratrol nanoparticles (RNs) elicited a neuroprotective effect in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, at significantly lower doses than unconjugated resveratrol (RSV) due to enhanced bioavailability. Furthermore, we demonstrated that the intranasal administration of a cell-derived secretome-based therapy at low concentrations leads to the selective neuroprotection of the optic nerve in EAE mice. The current study sought to assess the potential selective efficacy of lower concentrations of intranasal RNs for attenuating optic nerve damage in EAE mice. Methods: EAE mice received either a daily intranasal vehicle, RNs or unconjugated resveratrol (RSV) for a period of thirty days beginning on the day of EAE induction. Mice were assessed daily for limb paralysis and weekly for visual function using the optokinetic response (OKR) by observers masked to treatment regimes. After sacrifice at day 30, spinal cords and optic nerves were stained to assess inflammation and demyelination, and retinas were immunostained to quantify retinal ganglion cell (RGC) survival. Results: Intranasal RNs significantly increased RGC survival at half the dose previously shown to be required when given orally, reducing the risk of systemic side effects associated with prolonged use. Both intranasal RSV and RN therapies enhanced RGC survival trends, however, only the effects of intranasal RNs were significant. RGC loss was prevented even in the presence of inflammatory and demyelinating changes induced by EAE in optic nerves. Conclusions: The intranasal administration of RNs is able to reduce RGC loss independent of the inflammatory and demyelinating effects on the optic nerve and the spinal cord. The concentration of RNs needed to achieve neuroprotection is lower than previously demonstrated with oral administration, suggesting intranasal drug delivery combined with nanoparticle conjugation warrants further exploration as a potential neuroprotective strategy for the treatment of optic neuritis, alone as well as in combination with glucocorticoids. |
| first_indexed | 2024-04-24T10:42:44Z |
| format | Article |
| id | doaj.art-dc120eb8071f48c1b114600e71e7884f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:42:44Z |
| publishDate | 2024-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dc120eb8071f48c1b114600e71e7884f2024-04-12T13:20:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257404710.3390/ijms25074047Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple SclerosisEhtesham Shamsher0Reas S. Khan1Benjamin M. Davis2Kimberly Dine3Vy Luong4M. Francesca Cordeiro5Kenneth S. Shindler6Institute of Ophthalmology, University College London, London EC1V 9EL, UKScheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USAInstitute of Ophthalmology, University College London, London EC1V 9EL, UKScheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USAInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKScheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USAPurpose: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral administration of resveratrol nanoparticles (RNs) elicited a neuroprotective effect in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, at significantly lower doses than unconjugated resveratrol (RSV) due to enhanced bioavailability. Furthermore, we demonstrated that the intranasal administration of a cell-derived secretome-based therapy at low concentrations leads to the selective neuroprotection of the optic nerve in EAE mice. The current study sought to assess the potential selective efficacy of lower concentrations of intranasal RNs for attenuating optic nerve damage in EAE mice. Methods: EAE mice received either a daily intranasal vehicle, RNs or unconjugated resveratrol (RSV) for a period of thirty days beginning on the day of EAE induction. Mice were assessed daily for limb paralysis and weekly for visual function using the optokinetic response (OKR) by observers masked to treatment regimes. After sacrifice at day 30, spinal cords and optic nerves were stained to assess inflammation and demyelination, and retinas were immunostained to quantify retinal ganglion cell (RGC) survival. Results: Intranasal RNs significantly increased RGC survival at half the dose previously shown to be required when given orally, reducing the risk of systemic side effects associated with prolonged use. Both intranasal RSV and RN therapies enhanced RGC survival trends, however, only the effects of intranasal RNs were significant. RGC loss was prevented even in the presence of inflammatory and demyelinating changes induced by EAE in optic nerves. Conclusions: The intranasal administration of RNs is able to reduce RGC loss independent of the inflammatory and demyelinating effects on the optic nerve and the spinal cord. The concentration of RNs needed to achieve neuroprotection is lower than previously demonstrated with oral administration, suggesting intranasal drug delivery combined with nanoparticle conjugation warrants further exploration as a potential neuroprotective strategy for the treatment of optic neuritis, alone as well as in combination with glucocorticoids.https://www.mdpi.com/1422-0067/25/7/4047resveratrolneuroprotectiondemyelinating disease |
| spellingShingle | Ehtesham Shamsher Reas S. Khan Benjamin M. Davis Kimberly Dine Vy Luong M. Francesca Cordeiro Kenneth S. Shindler Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis International Journal of Molecular Sciences resveratrol neuroprotection demyelinating disease |
| title | Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis |
| title_full | Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis |
| title_fullStr | Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis |
| title_full_unstemmed | Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis |
| title_short | Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis |
| title_sort | intranasal resveratrol nanoparticles enhance neuroprotection in a model of multiple sclerosis |
| topic | resveratrol neuroprotection demyelinating disease |
| url | https://www.mdpi.com/1422-0067/25/7/4047 |
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