Developing brain-targeting liposomes to deliver mesenchymal stem cells secretome for Parkinson’s Disease Regenerative Medicine

Jun 28, 2022, 12:10 PM
10m
Room: S2

Room: S2

Speaker

Barata-Antunes, Sandra (Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and ICVS/3B’s – PT Government Associated Laboratory, Braga/Guimarães)

Description

Parkinson's disease (PD) is a neurodegenerative disease clinically characterized by motor disabilities. Current therapies are not being fully effective. Remarkably, the neuroregulatory molecules secreted by mesenchymal stem cells (MSCs) have been suggested as an alternative therapy. However, direct injection into the brain is the delivery approach that has been used in pre-clinical models. Thus, the main goal of this work was to develop brain-targeting liposomes to deliver the secretome of MSCs and allow a systemic delivery treatment. For that, liposomes were functionalized with lactoferrin (Lf), whose receptors are overexpressed in endothelial cells present at blood brain barrier, as well as in dopaminergic neurons at substantia nigra, in both animal models and PD patients. The particle size distribution, polydispersity index (PDI) and zeta potential of liposomes were assessed by Dynamic Light Scattering (DLS). An in vitro release profile study was performed to predict the in vivo bioperformance of MSC secretome-loaded liposomes. To determine the effect of the liposomes on cell viability, MTS assay was performed using SH-SY5Y cells. The DLS results presented hydrodynamic diameters around 100 nanometers and relatively low PDI values. Liposomes were able to encapsulate the MSC secretome, allowing a sustained release profile. MTS assay demonstrated that liposomes did not induce alterations on viability of SH-SY5Y cells. SH-SY5Y cells were differentiated into a mature dopaminergic neuronal phenotype and exposed to the neurotoxin 6-hydroxidopamine to reproduce an in vitro cell model of PD. Lf-modified MSC secretome-loaded liposomes were able to protect the viability of these cells after neurotoxin exposure. A biodistribution study was performed in mice using Texas Red-labelled liposomes, 5 hours after intravenous administration. The study showed that Lf-modified liposomes were detected on the brain of mice in a higher concentration, when compared to the liposomes that were not functionalized. Remarkably, intravenous treatment of Lf-modified MSC secretome-loaded liposomes were able to improve motor disabilities in a mice model of PD. These results highlight the potential of MSC secretome-loaded liposomes to function as a brain-targeting delivery system therapy for PD.

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