Mursaleen, L;
Noble, B;
Somavarapu, S;
Zariwala, MG;
(2021)
Micellar nanocarriers of hydroxytyrosol are protective against parkinson’s related oxidative stress in an in vitro hcmec/d3‐sh‐sy5y co‐culture system.
Antioxidants
, 10
(6)
10.3390/antiox10060887.
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Abstract
Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suita-ble characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferox-amine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3‐SH‐SY5Y co‐culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p < 0.0001, n = 6). This resulted in increased protection against rotenone induced cyto-toxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p < 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD‐related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models.
| Type: | Article |
|---|---|
| Title: | Micellar nanocarriers of hydroxytyrosol are protective against parkinson’s related oxidative stress in an in vitro hcmec/d3‐sh‐sy5y co‐culture system |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/antiox10060887 |
| Publisher version: | https://doi.org/10.3390/antiox10060887 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | Hydroxytyrosol; deferoxamine; Parkinson’s disease; oxidative stress; antioxidant; neurodegeneration; blood–brain barrier; Transwell®; Pluronic® F68; dequalinium; micelles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices 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 Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10129442 |
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