It is challenging to develop effective disease-modifying therapies for neurological diseases such as Alzheimer’s disease because drugs must cross the blood-brain barrier to affect the brain.
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As only a small portion of a dose will make it through the barrier, the doses administered must be high. This means that significant side effects are often experienced, which can make them unsuitable.
To overcome this issue, scientists at the Institut national de la Recherche Scientifique (NRS) have developed an innovative drug delivery system that utilizes polymer-coated nanoparticles to increase the chances of the drug molecules crossing the blood-brain barrier. The new method could help develop new, urgently needed treatments for Alzheimer’s disease.
12.7 Million Americans are Predicted to be Living With Alzheimer’s Disease By 2050
Around 6.2 million Americans are currently living with Alzheimer’s disease. A figure that is set to rise significantly to 12.7 million by 2050. Currently, there is no cure for the disease. Nor is there any approved disease-modifying therapy capable of altering the disease course. The only therapeutics available currently are targeted at reducing the symptoms only.
Due to the disease’s prevalence and the rapid rate at which numbers are expected to rise as the population ages, the approval of disease-modifying therapy, one that can impact the progression of the disease, is urgently needed.
Nanoparticle Coatings Enhance Drug Delivery
In a recent study published in the journal Biomaterials in October 2021, a team of scientists led by Jean-Michel Rabanel, under the supervision of Charles Ramassamy, conducted a study that demonstrated the efficacy of new polymer-coated nanoparticles in improving drug permeability across the blood-brain barrier and enhancing the delivery of encapsulated drugs in the brain.
The researchers investigated the impact of two different polymer coatings on a biocompatible material - polylactic acid (PLA) nanoparticles (suitable for drug delivery due to their rapid degradation and clearance from the body).
Polyethylene glycol (PEG) was the first coating. Already, this material had proven its potential via studies utilizing zebrafish, an animal with a transparent body, making it possible to visualize the distribution of the nanoparticles in real-time. The second coating was a zwitterionic polymer, which was studied under the same conditions.
The team was able to show that the second coating, the zwitterionic polymer, had better access to the brain. However, they also found that the coating was more readily absorbed into the walls of the blood vessels, thus reducing their circulation time.
Therefore, the team concluded that PEG shows the most potential as a polymer coating for delivering drugs across the blood-brain barrier to move it rapidly through the bloodstream. On the other hand, it was theorized that the zwitterionic polymer might induce a weaker immune system response.
It was suggested that a mixture of the two coatings could potentially produce the best results, leveraging the benefits of each of the nanostructures.
The findings of the study highlight the crucial role played by drug coatings on the efficacy and safety profiles of drugs. Exploring how coatings can impact the pharmacodynamics and pharmacokinetics of a therapeutic will no doubt propel the use of nanoparticles in the field of pharmaceuticals, particularly for the development of new therapeutics to tackle neurological diseases where drugs need to efficiently pass through the blood-brain barrier.
The Future of Nanoparticles in the Development of New Alzheimer’s Drugs
In the near future, we can expect many groundbreaking developments to emerge from nanoparticle research in the field of drug development for Alzheimer’s disease and other neurodegenerative diseases such as Parkinson’s disease. The new research discussed here is just one of many newly emerging studies that have demonstrated the potential therapeutic use of nanoparticles in Alzheimer’s treatments.
In December of 2021, for example, scientists at Vanderbilt University Medical Center discovered a new type of nanoparticle known as a ‘supermere’ that is realized from cells and contains enzymes, proteins, and RNA.
This material contained by the supermeres has been associated with a range of diseases, including Alzheimer’s disease, many types of cancer, cardiovascular disease, and even COVID-19. While the research is in its early stages, there is a potential for these nanoparticles to be used as biomarkers for diseases, such as Alzheimer’s disease. Such a biomarker would help with diagnosis and monitoring the treatment efficacy.
Overall, this research aiding the growth of the emerging field of nanomedicines. It is likely that research into the use of nanoparticles for treating brain diseases like Alzheimer’s disease will encourage further interest in the area of nanomedicines, which will potentially help it develop to establish new medicines for a range of disorders.
Nanomedicine has the opportunity to develop new therapeutic options for diseases that may currently have no cure or no disease-modifying therapy available. Many diseases, like Alzheimer’s disease, are currently limited to treating the symptoms only, something that must change in order to enhance patient outcomes and quality of life.
Continue reading: Progressing Pulmonary Drug Delivery with Nanoparticles.
References and Further Reading
Khan, N., Mir, M., Ngowi, E., Zafar, U., Khakwani, M., Khattak, S., Zhai, Y., Jiang, E., Zheng, M., Duan, S., Wei, J., Wu, D. and Ji, X., (2021) Nanomedicine: A Promising Way to Manage Alzheimer’s Disease. Frontiers in Bioengineering and Biotechnology, 9. Available at: https://www.frontiersin.org/articles/10.3389/fbioe.2021.630055/full
Rabanel, J., Faivre, J., Zaouter, C., Patten, S., Banquy, X. and Ramassamy, C., (2021). Nanoparticle shell structural cues drive in vitro transport properties, tissue distribution and brain accessibility in zebrafish. Biomaterials, 277, p.121085. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0142961221004415?via%3Dihub
Zhang, Q., et al (2021). Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets. Nature Cell Biology,. Available at: https://www.nature.com/articles/s41556-021-00805-8