Periodic Reporting for period 1 - Dual-NanoMAE (Dual action Nanoparticles using MicroAlgae extracts for chronic ulcers)
Periodo di rendicontazione: 2021-07-12 al 2023-07-11
Biomaterials based on natural substances are playing an increasingly important role in the development of new products for medical applications and therapies (Schilrreff & Alexiev, 2022). Specifically, the use of natural antioxidants integrated into innovative biomaterials holds significant potential for the development of future therapeutics, especially in wound healing. In general, wound healing is inhibited when the wound remains in the inflammatory stage for too long and thus becomes chronic (Schilrreff & Alexiev, 2022). The most common chronic wounds include pressure ulcers, diabetic ulcers, venous ulcers and chronic non-healing wounds due to trauma or surgical wounds. Chronic wounds occur at the molecular level when enzymes in the wound bed are not in balance, oxidative stress occurs, or when bacteria colonize and form biofilms. Oxidative stress is mainly due to the formation of free radicals. The body's natural antioxidant capacity, which is no longer sufficient in the context of oxidative stress in the clinical picture, can be compensated by the supply of antioxidants. Various biomaterials with integrated antioxidants have been described to promote wound healing and skin tissue regeneration (Schilrreff and Alexiev, 2022). Promising results have been shown in animal studies, leading to the first commercial wound healing products. However, clinical studies in humans are still very limited. This is mainly due to the poor water solubility and thus bioavailability/stability of natural antioxidants, which is a major obstacle to their widespread therapeutic use. Several strategies to improve these negative properties have been investigated. Mostly, these are nanoparticle-based strategies that can improve poor water solubility (Simioni, 2022). In addition to water solubility and bioavailability, the varying antioxidant activity of these substances is currently still a major problem, which also limits the success of their therapeutic use. For example, curcumin has an antioxidant capacity of n~3 (n is the number of radical molecules that can be neutralised by one molecule of antioxidant, therefore also called stoichiometry). The value for vitamin E is n=2-3. A higher antioxidant capacity is attributed to astaxanthin and the carotenoids in general (Tsuchiya, 1992), and thus also a broad effect (Schilrreff & Alexiev, 2022). However, the antioxidant capacity data for astaxanthin in particular vary greatly in the literature or are only given in relative terms (Dose, 2016).
To address this need, this research project focused on the remarkable properties of the highly antioxidative astaxanthin compound from the green microalgae Chlorella zofingiensis, its combination in a new therapeutic lipid nanoparticle together with an accurate determination of its antioxidant capacity.
To address this need, this research project focused on the remarkable properties of the highly antioxidative astaxanthin compound from the green microalgae Chlorella zofingiensis, its combination in a new therapeutic lipid nanoparticle together with an accurate determination of its antioxidant capacity.
The key factors that will drive the growth of the biomaterials market in the coming years are the increasing prevalence of chronic diseases, such as diabetes, which is associated with chronic wounds that lead to amputations if not healed in time, the increasing ageing of the population, which is associated with a general increase in oxidative stress, and the increasing demand for biocompatible materials.
Powerful antioxidants derived from natural sources are good candidates for these therapeutic treatments. However, their use in clinical use is compromised by the high instability and low solubility. One way of making these antioxidants more suitable for therapies is their formulation with the help of lipid nanoparticles. The effect of the lipid matrix on natural bioactive compounds entrapment, antioxidant capacity and storage stability are key to successfully engineer nanomaterials with specific performance properties. Furthermore, astaxanthin's biological effect in reducing oxidative stress depends on the antioxidant effect of the final product and its maintenance during the extraction process and storage.
Therefore, the main scientific achievements during the fellowship are based on:
1) the development for the first time of an assay that can reproducibly determine the antioxidant capacity of astaxanthin (synthetic, natural, from food supplements, even extracted from microalgae) in absolute stoichiometric values,
2) the use of an astaxanthin extracted from microalgae with a high antioxidant capacity,
3) encapsulation in nanostructured lipid nanoparticles, which at the same time benefits from the natural soluble lipids of microalgae.
Overall, the project has developed Dual-NanoMAE nanoparticles and an assay for the quantitative and reproducible determination of the antioxidant capacity of astaxanthin, with potential for exploitation. We have currently initiated a market analysis study, where Dr Schilrreff is acting as principal investigator in a project that will give us the opportunity to validate our research results in terms of their application-orientation and to increase exploitation opportunities. A patent is being considered. Finally, the technology developed by Dual-NanoMAE will be disseminated in a series of publications in preparation.
Powerful antioxidants derived from natural sources are good candidates for these therapeutic treatments. However, their use in clinical use is compromised by the high instability and low solubility. One way of making these antioxidants more suitable for therapies is their formulation with the help of lipid nanoparticles. The effect of the lipid matrix on natural bioactive compounds entrapment, antioxidant capacity and storage stability are key to successfully engineer nanomaterials with specific performance properties. Furthermore, astaxanthin's biological effect in reducing oxidative stress depends on the antioxidant effect of the final product and its maintenance during the extraction process and storage.
Therefore, the main scientific achievements during the fellowship are based on:
1) the development for the first time of an assay that can reproducibly determine the antioxidant capacity of astaxanthin (synthetic, natural, from food supplements, even extracted from microalgae) in absolute stoichiometric values,
2) the use of an astaxanthin extracted from microalgae with a high antioxidant capacity,
3) encapsulation in nanostructured lipid nanoparticles, which at the same time benefits from the natural soluble lipids of microalgae.
Overall, the project has developed Dual-NanoMAE nanoparticles and an assay for the quantitative and reproducible determination of the antioxidant capacity of astaxanthin, with potential for exploitation. We have currently initiated a market analysis study, where Dr Schilrreff is acting as principal investigator in a project that will give us the opportunity to validate our research results in terms of their application-orientation and to increase exploitation opportunities. A patent is being considered. Finally, the technology developed by Dual-NanoMAE will be disseminated in a series of publications in preparation.
This MSCA project aimed to perform multidisciplinary research for better understanding the antioxidant capacity of astaxanthin and make it more suitable for therapies in its formulation with the help of lipid nanoparticles.
Innovative aspects included / achieved:
I, using nanomedicine technologies for more efficient entrapment of natural bioactive compounds such as astaxanthin. This could ultimately serve as a platform for other natural hydrophobic molecules. This strategy is appealing to both the scientific and industrial community. The key factors that will drive the growth of the bio/nanomaterials market in the coming years are the increasing prevalence of chronic diseases, such as diabetes, which is associated with chronic wounds leading to amputations if not healed in time, the growing aging population, which is associated with an overall increase in oxidative stress, and the increasing demand for biocompatible materials.
Nanoparticles with astaxanthin are designed to increase the pharmaceutical availability of the hydrophobic compound astaxanthin and improve the bioavailability and chemical stability that are normally low and limit its use to date. This research may fill a gap in the market for non-invasive antioxidant medical devices. The potential of the Dual-NanoMAE project results to be transferred to the industry will support Europe in the lead on sustainable industries and serve as a demonstration of successful multi-disciplinary research. For this reason, the next project, as an extension of MSCA, is being funded by Provalid, IBB GmbH with the aim to validate our research results with respect to their application orientation and to increase exploitation opportunities.
II, establishment of an optimized method to correctly and accurately analyze and characterize the antioxidant capacity of astaxanthin, and similar compounds, and advance the research and development of successful nanomedicines. Having functional and satisfactory methods to analyze antioxidant capacity is a key point in this field.
This activity has the potential to apply together for a patent, with the potential of future commercialization.
Innovative aspects included / achieved:
I, using nanomedicine technologies for more efficient entrapment of natural bioactive compounds such as astaxanthin. This could ultimately serve as a platform for other natural hydrophobic molecules. This strategy is appealing to both the scientific and industrial community. The key factors that will drive the growth of the bio/nanomaterials market in the coming years are the increasing prevalence of chronic diseases, such as diabetes, which is associated with chronic wounds leading to amputations if not healed in time, the growing aging population, which is associated with an overall increase in oxidative stress, and the increasing demand for biocompatible materials.
Nanoparticles with astaxanthin are designed to increase the pharmaceutical availability of the hydrophobic compound astaxanthin and improve the bioavailability and chemical stability that are normally low and limit its use to date. This research may fill a gap in the market for non-invasive antioxidant medical devices. The potential of the Dual-NanoMAE project results to be transferred to the industry will support Europe in the lead on sustainable industries and serve as a demonstration of successful multi-disciplinary research. For this reason, the next project, as an extension of MSCA, is being funded by Provalid, IBB GmbH with the aim to validate our research results with respect to their application orientation and to increase exploitation opportunities.
II, establishment of an optimized method to correctly and accurately analyze and characterize the antioxidant capacity of astaxanthin, and similar compounds, and advance the research and development of successful nanomedicines. Having functional and satisfactory methods to analyze antioxidant capacity is a key point in this field.
This activity has the potential to apply together for a patent, with the potential of future commercialization.