Shamsher, Ehtesham;
(2021)
Formulation of potential phytochemicals with neuroprotective action for the treatment of Alzheimer's disease, glaucoma and multiple sclerosis.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
PURPOSE: Neurodegenerative diseases such as Alzheimer’s disease (AD), glaucoma and multiple sclerosis (MS) are characterised by the death of neuronal cells. Resveratrol and curcumin are polyphenols with neuroprotective effects but a low bioavailability. My aim was to develop novel nanoparticle formulations of these polyphenols and, assess them in vitro and in vivo. METHODS: Resveratrol and curcumin were formulated independently into nanoparticles. These formulations were assessed for neuroprotection on rat retinal precursor cells (R28) used as an RGC model. Next, a triple transgenic AD (3xTg-AD) mouse model was treated with either resveratrol or curcumin nanoparticles (RNs or CNs) intranasally 5 days/week for 3 months. In the rat ocular hypertension (OHT) glaucoma model, RNs were given topically daily for 3 weeks. RNs were also given intranasally in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) daily for 1 month. After sacrifice, retinas were labelled with an RGC marker (Brn3a) in all models. In 3xTg-AD mice, brains were immunostained for amyloid-beta (Aβ) and phospho-tau (pTau). In the EAE model, optic nerves and spinal cords were stained to detect inflammation and demyelination. RESULTS: RNs and CNs had an encapsulation efficiency >70%. They were neuroprotective against glutamate excitotoxicity and hypoxia in vitro. They showed a reduction of Aβ and pTau deposition in the brain of 3xTg-AD mice but had no effect on RGC loss. In the OHT model, RNs reduced RGC loss after 3 weeks of treatment. Finally, RNs also reduced RGC loss in the EAE model after 1 month of treatment without any effect on the optic nerve and spinal cord inflammation and demyelination. CONCLUSIONS: Nanoparticle formulations increase resveratrol and curcumin solubility. They show neuroprotection in vitro and in vivo. They could be used as a paradigm shift in the treatment of neurodegenerative diseases. However, further experiments are necessary before clinical application.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Formulation of potential phytochemicals with neuroprotective action for the treatment of Alzheimer's disease, glaucoma and multiple sclerosis |
| Event: | UCL (University College London) |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10137974 |
Archive Staff Only
 |
View Item |
