Nano-enabled phytocomplexes could help prevent neurodegeneration
Phytochemicals are bioactive chemical compounds produced naturally by plants. “While not strictly essential nutrients, many phytochemicals generate the beneficial properties of fruits, vegetables, herbs and other plant-derived products,” explains Sergiy Lyubchyk(opens in new window), coordinator of the PhytoAPP(opens in new window) project, from Lusófona University(opens in new window), Portugal. PhytoAPP, undertaken with the support of the Marie Skłodowska-Curie Actions(opens in new window) programme, was interested in phytochemicals because some plant-derived molecules offer the potential to protect cells against the processes associated with neurodegenerative diseases, such as oxidative stress, inflammation and abnormal protein aggregation. The EU-funded project was focused on improving the stability, solubility and biological availability of these compounds by developing new nano-enabled ‘phytomaterials’. “We have bridged the gap between an ambitious scientific idea and a proof of concept, using nanotechnology to redesign promising but difficult-to-use phytochemicals into a more water-soluble and biologically relevant form,” says Lyubchyk. “This opens up the possibility of future phytochemical-based products to prevent neurodegeneration.”
Developing water-soluble nano-enabled phytocomplexes
A key limitation of many promising natural compounds for health-related applications, is their low water solubility. When compounds don’t dissolve well in water, it is difficult for the body to absorb, transport and use them effectively. “Our answer was to use nanotechnology to improve the aqueous behaviour of the phytochemical component, while preserving or even enhancing its biological relevance,” explains Lyubchyk. The team designed phytocomplexes where fullerene C60(opens in new window), a nanoscale spherical carbon structure, interacts with plant-derived dihydroquercetin(opens in new window) molecules, improving their behaviour and functional properties in water. “Nanotechnology was essential to rethinking how phytochemicals can be formulated, stabilised and, in the future, potentially delivered in biological systems,” adds Lyubchyk. After optimising these water-soluble fullerene–phytochemical complexes, the team explored their structure and physicochemical properties. This included physicochemical characterisation of the materials, in vitro bioactivity and nanotoxicity assessments, antioxidant and cytoprotective testing and kinetic studies of amyloid fibril formation(opens in new window). The amyloid-related tests were vital because abnormal protein aggregation is present in several neurodegenerative diseases. “Our phytocomplexes increased the time lag for amyloid fibril formation and reduces the total amount of fibrils formed,” notes Lyubchyk. Preclinical studies were then carried out using Alzheimer’s- and Parkinson’s-related models to assess the safety and suitability of the phytocomplexes. The models enabled the team to explore the biological effects of the phytocomplexes, including behavioural, histological, molecular and blood-brain-barrier-related aspects, in disease-relevant systems. “What we achieved is a proof of concept validated formulation based on the C60–dihydroquercetin phytocomplex. We’ve demonstrated that this early-stage material merits further development and testing for future preventive health, nutraceutical or biomedical applications,” says Lyubchyk.
At the cutting edge of future preventative healthcare
PhytoAPP’s achievements support a number of EU health-related ambitions, including the development of innovative health solutions(opens in new window) that improve health outcomes and quality of life. The results also contribute to research into advanced materials. Alongside nano-enabled phytochemical formulations for health products, likely future applications include wider nutraceutical or biomedical research applications and further development of safe-by-design nanomaterials. “While the research remains at a preclinical/prototype stage, it has provided the scientific and technological basis for future products that may support healthy ageing and prevention-oriented strategies for neurodegenerative conditions,” remarks Lyubchyk. Towards this end, the team are continuing their validation work, while expanding preclinical testing to progress from a laboratory prototype towards a more mature product. Meanwhile, commercialisation options are also being explored, including the assessment of regulatory requirements and the protection of intellectual property rights.