Yealland, G;
Battaglia, G;
Bandmann, O;
Mortiboys, H;
(2016)
Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes.
Neuroscience Letters
, 630
pp. 23-29.
10.1016/j.neulet.2016.06.065.
Preview |
Text
1-s2.0-S0304394016304748-main.pdf - Published Version Download (1MB) | Preview |
Abstract
Mutations in parkin cause autosomal recessive Parkinsonism and mitochondrial defects. A recent drug screen identified a class of steroid-like hydrophobic compounds able to rescue mitochondrial function in parkin-mutant fibroblasts. Whilst these possess therapeutic potential, the size and high hydrophobicity of some may limit their ability to penetrate the blood-brain barrier from systemic circulation, something that could be improved by novel drug formulations. In the present study, the steroid-like compounds Ursolic Acid (UA) and Ursocholanic Acid (UCA) were successfully encapsulated within nanoscopic polymersomes formed by poly(2-(methacryloyloxy)ethyl phosphorylcholine)–poly(2-di-isopropylamino)ethyl methacrylate) (PMPC-PDPA) and separated into spherical and tubular morphologies to assess the effects of nanoparticle mediated delivery on drug efficacy. Following incubation with either morphology, parkin-mutant fibroblasts demonstrated time and concentration dependent increases in intracellular ATP levels, resembling those resulting from treatment with nascent UA and UCA formulated in 0.1% DMSO, as used in the original drug screen. Empty PMPC-PDPA polymersomes did not alter physiological measures related to mitochondrial function or induce cytotoxicity. In combination with other techniques such as ligand functionalisation, PMPC-PDPA nanoparticles of well-defined morphology may prove a promising platform for tailoring the pharmacokinetic profile and organ specific bio-distribution of highly hydrophobic compounds.
| Type: | Article |
|---|---|
| Title: | Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neulet.2016.06.065 |
| Publisher version: | http://dx.doi.org/10.1016/j.neulet.2016.06.065 |
| Language: | English |
| Additional information: | © 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Parkinson's disease, Mitochondria, Parkin, Polymersome, Anisotropic nanoparticle, Pmpc-pdpa, Advanced Solid Tumors, Blood-brain-barrier, Ursolic Acid, Intracellular Delivery, Cancer Cells, In-vitro, Nanoparticles, Disease, Mice, Size |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1506141 |
Archive Staff Only
 |
View Item |
