Press Release, July 2019
Second article published in renowned scientific journal ACS Nano
Resulting from the High on Nano project, a second study is just published in the renowned scientific journal ACS Nano. This is a continuation of the former study, where the research group already showed that the indigenous biomaterial hyaluronic acid (HA) can be efficiently developed into nanoparticles, offering a highly biocompatible delivery platform for targeted imaging and precision therapy of atherosclerosis (see the press release). In this new study, that was co-funded by Sensi Pharma, a next step was taken to better understand the details of the trafficking of these HA nanoparticles into the atherosclerotic plaque. A better comprehension of the characteristics of this platform will aid in the application of endo-cannnabinoid based nanoparticles in research, such as the recently started NAVISTROKE research program, and eventually the clinic.
As described in the former ACS Nano publication the research group used HA nanoparticles to target atherosclerotic plaques in experimental models. They showed that this nanoparticle platform offers beneficial characteristics for the accurate and efficient delivery of therapeutic and diagnostic compounds, including cannabinoids and related ligands, to atherosclerotic lesions. This was a result of favourable pharmacokinetics, cost effectiveness and the high affinity of these nanoparticles for immune cells within the atherosclerotic plaque.
Based on these promising results, the research group decided to take a next step in the further investigation and characterization of this delivery platform, to better understand the trafficking of the systemically administered HA nanoparticles. The relevance of this study is underlined by the fact that the specific pathways of nanoparticle trafficking to atherosclerotic plagues are still poorly understood, and only a small number of studies have been focusing on this topic.
This last study focused specifically on the endothelium, the layer of cells lining the blood vessels under which the atherosclerotic plaque and resulting inflammation is located (see picture below).
Using state of the art imaging techniques the authors show that the endothelium is highly dynamic, and that the trafficking of the HA nanoparticle is highly dependent on the degree of endothelial dysfunction. Additionally, it is shown that treatment with a compound aimed at endothelial normalization via inhibition of cellular metabolism, limits the ability of HA nanoparticles to migrate to the atherosclerotic plaque. These results highlight the importance of the endothelial barrier in nanoparticle trafficking across the atherosclerotic endothelium, and will thereby also have a large impact on the application of endocannabinoid-based nanomedicine in atherosclerosis.
All this new knowledge is now used and applied in the recently started NAVISTROKE project (see our blogpost of last June directly below), spanning several universities in the Netherlands, Germany, and the USA. In this project nanomedicine will be combined with a range of therapeutic and diagnostic compounds, including natural and synthetic cannabinoids, with the purpose to deploy the anti-inflammatory effects of cannabinoids to limit the damage after a stroke. Keep an eye on our blog to stay up to date with the developments.
Progress, June 2019
Scientific Research Project NAVISTROKE Fully Up and Running
Every year, approximately 43,000 people suffer a stroke. In case of a stroke, part of the brain receives insufficient oxygen. This leads to the failure of important brain functions, and in many cases, even to death. The scientific research project Navistroke was set up to tackle this important social problem. Navistroke’s goal is to deploy the anti-inflammatory effects of cannabinoids to limit the damage after a stroke.
In order to achieve this goal, a grant was awarded by the Netherlands Organisation for Scientific Research (NWO) in order to achieve a collaboration between universities and the industry. This collaboration consists of research groups of Leiden University, Amsterdam UMC and the University Medical Center Utrecht. This team of researchers is joined by the industrial partners Sensi Pharma and Enceladus and is supported by experts in the areas of (endo-)cannabinoids, immunology, nanomedicine and neurology.
This collaboration combines expertise on the entire process from the development of new medication, to the application in the hospital. Leiden University is developing new substances that make optimal use of the anti-inflammatory properties of the endo-cannabinoid system. The Amsterdam UMC then develops nanoparticles that contain these substances. These particles ensure that substances reach the cells of the immune system specifically, where they can deploy their anti-inflammatory effects. These cannabinoid nanoparticles are then applied at the University Medical Center Utrecht, where the disease process of a stroke can be followed via MRI techniques. The industrial partner Sensi Pharma supports this research team with their expertise in the field of natural cannabinoids, and the biotech company Enceladus provides know-how regarding the clinical application of nanoparticles.
Research has now started in each of the three locations. A researcher was appointed at every location to work on the Navistroke project as a PhD student. The project will take a total of 5 years, and the goal is to develop a novel medicine that can be applied in the treatment of stroke.
Press Release, May 2017
Crowd funded High On Nano reaches first crucial milestone
AMSTERDAM – On May 2nd 2017, the High On Nano project reached an important milestone, as a first set of scientific results were published in the high-impact journal ACS Nano. The study was partially funded by Sensi Pharma BV, a company that was established to solidify High on Nano’s success in 2014, and is aimed at developing and applying natural cannabinoids for medical purposes. Using natural molecular building blocks, an international research team, spearheaded by investigators from the Academic Medical Center of the University of Amsterdam, shows that hyaluronan-based nanoparticles (HA-NPs) can be employed to molecularly image atherosclerosis-associated inflammation as well as to effectively ameliorate atherosclerosis. Atherosclerosis is the underlying cause of cardiovascular disease, including heart attack and stroke, and represents the highest expenditure in the world health care.
This research, led by the ‘High on Nano’ PhD student Thijs Beldman, is the result of a collaboration between eight universities. The investigators show that the indigenous biomaterial hyaluronan acid (HA) can be developed into nanoparticles and used to target atherosclerotic plaques in experimental models. The study shows that HA-NPs are a highly biocompatible delivery platform for targeted imaging and precision therapy of atherosclerosis, due to their high affinity for immune cells, with a 6- to 40-fold higher uptake of radiolabelled HA-NPs by aortic white blood cells compared to white blood cells from normal tissue. Additionally, it was demonstrated that the HA-NPs also exert atheroprotective effects, by decreasing the immune cell infiltration.
The hyaluronan polymer is an interesting building block, owing to its cost-effective production and distinctive physicochemical and biological properties. The biological activity of HA, however, strongly depends on the degree of polymerization, while its application is challenging due to rapid blood clearance and the way it reacts with water. The group hypothesised that hyaluronan can be formulated into nanoparticles that display improved tunability to cellular interactions and profoundly improved pharmacokinetic properties.
The next step is to further investigate how the diagnostic and therapeutic effects of this cost-efficient drug delivery platform can be used to efficiently deliver cannabinoids in atherosclerosis and other diseases. Cannabinoids also have some interesting anti-inflammatory properties, and combining them with drug delivery platforms, such as HA-NPs, may improve their specificity, bioavailability and resulting efficacy, while simultaneously reducing adverse effects, potentially increasing their clinical utility.
High on Nano is a non-profit organisation, founded in 2013, with the aim to familiarize the general public with the work of Willem Mulder’s research group in general and the possibilities of cannabinoid nanoparticles for biomedical purposes specifically. www.highonnano.com
Sensi Pharma is a privately owned Dutch company, manufacturing specialized pharmaceutical products. It was founded in 2014, shortly after the first crowd fund success of High on Nano. It focuses on the application of natural cannabinoids for medical purposes, and works together with renowned scientists in the field of Nanomedicine, Medicinal Chemistry, Drug Discovery, and Biomedical MR Imaging for development. www.sensipharma.com