The effective treatment of Alzheimer’s disease has been relatively stunted, with most drugs only treating symptoms with relatively low success. Advancements in biomaterials and regenerative medicine technologies are offering novel ways of improving drug delivery to affected regions of the brain with a controlled release of drugs.
A research group from the University of Barcelona have used biomaterials in the form of nanoparticles, to optimise the treatment of Alzheimer’s disease. The team have encapsulated a licensed Alzheimer’s drug, memantine, in a biodegradable nanoparticle.
The nanoparticle acts as a vehicle for drug delivery, with a poly-ethylene glycol (PEG) coated surface which is effectively a chemical pass code for the blood-brain barrier, allowing for the nanoparticle – with drug encapsulated within – to enter the brain.
PEG Nanoparticles And Memantine
The PEG-nanoparticle and memantine treatment improved the memory capabilities of mice with an Alzheimer’s disease mutation compared to the drug alone, whilst also reducing the amount of amyloid-beta plaques and associated neuroinflammation common to Alzheimer’s disease brains. These results show that with improved and effective administration of Alzheimer’s disease drugs it is possible to elicit a disease modifying effect.
The degradation of the nanoparticle over time allows for controlled release of the drug once it has entered the brain tissue, allowing for the drug to be administered less frequently than when it is administered without nanoparticles; reducing the chances of any adverse toxicities.
In addition to this, analysis of memantine clinical trials have shown only a slight improvement in cognition, but with increased efficiency of drug dosing through use of nanoparticles to increase drug action at its target could increase the drugs effect.
The researchers found that the PEG-nanoparticle and memantine combination was able to cross the blood-brain barrier in both the mouse model and a lab based cell model, with the cell model establishing that the drug nanoparticle combination was not toxic to the neurovascular cells of the brain.
These promising results may lead to the more effective administration of memantine for treatment of Alzheimer’s disease, with nanoparticles optimising the delivery of the drug and duration of drug effect on the brain. The ability of nanoparticle bound memantine to treat neuroinflammation and amyloid-beta plaque build-up could offer a solution to the dwindling drug discovery pipeline for Alzheimer’s disease.
In addition to this, whilst memantine was used in this study, the nanoparticle approach could be applied to any number of Alzheimer’s disease drugs to improve blood-brain barrier transport and dosing regimens.
This could lead to previously inefficient drugs which have otherwise promising preclinical testing being used in a nanoparticle therapy to rejuvenate the Alzheimer’s disease drug discovery pipeline.
Sánchez-López, E., Ettcheto, M., Egea, M.A. et al.
Memantine loaded PLGA PEGylated nanoparticles for Alzheimer’s disease: in vitro and in vivo characterization
J Nanobiotechnol (2018) 16: 32. https://doi.org/10.1186/s12951-018-0356-z
Author: Geoffrey Potjewyd; Regenerative Medicine & Neuroscience PhD student at the University of Manchester.
Image: Sánchez-López, E., et al. CC-BY. Hipocampus of WT mice with PLGA-Rho nanoparticles.