Periodic Reporting for period 1 - CryForm (Crystal Engineering the New Generation of Sustainable, Biocompatible and Stimuli Responsive Formulations for the Delivery of Active Ingredients)
Período documentado: 2021-10-01 hasta 2023-03-31
This ERC starting grant 2020 “Crystal Engineering the New Generation of Sustainable, Biocompatible and Stimuli Responsive Formulations for the Delivery of Active Ingredients” (CryForm) project will develop innovative natural crystals for the design of new formulations easily soluble and able to deliver active ingredients in a controlled way, to be used in the agrochemical, pharmaceutical and food industry.
Description of the research project
Recent progress in pharmacology and biotechnology has led to a dramatic increase in power and specificity of new generation drugs, active agrochemical ingredients and food nutraceuticals. At the same time, a problem remains in making these substances water soluble, because of their high molecular weight and complex structure. Multiphase systems (such as emulsions, foams and creams) can solve this problem but are traditionally produced with synthetic stabilizing agents, which can make them unsafe and contribute to CO2 production.
Cryform aims at replacing synthetic stabilizing agents with crystalline materials that are natural, biocompatible and biodegradable, that can enable the design of innovative multiphase formulations.
The project has three fundamental objectives that will make this “revolution” possible: the study of the relation between crystalline structure and macroscopic properties of solid particles, the analysis of the thermodynamic and kinetic mechanisms of crystal nucleation and growth, as well as and the understanding of the role of large biomolecules in in the kinetic stability of solid crystals.
These elements will allow substantial progress of the current fundamental understanding of crystallization of organic materials and allow the development of formulations that can be used for pharmaceutical, agrochemical and food products that are safer, more sustainable and also more affordable.
Impact on society
The project tackles a major crystal engineering challenge and will generate new knowledge essential for the whole crystallization community. In particular, it will enable the design of biocompatible, safe and sustainable crystals to be used for pharmaceutical and cosmetic formulations, and to develop new products for the food and agriculture industry that are able of controlled release of active ingredients.
In general, the project will contribute to the development of more sustainable manufacturing processes also at the industrial scale and will help the transition of the European Union to a modern and competitive economy, efficiently using resources, as it is necessary to achieve the European Green Deal.
Description of the research project
Recent progress in pharmacology and biotechnology has led to a dramatic increase in power and specificity of new generation drugs, active agrochemical ingredients and food nutraceuticals. At the same time, a problem remains in making these substances water soluble, because of their high molecular weight and complex structure. Multiphase systems (such as emulsions, foams and creams) can solve this problem but are traditionally produced with synthetic stabilizing agents, which can make them unsafe and contribute to CO2 production.
Cryform aims at replacing synthetic stabilizing agents with crystalline materials that are natural, biocompatible and biodegradable, that can enable the design of innovative multiphase formulations.
The project has three fundamental objectives that will make this “revolution” possible: the study of the relation between crystalline structure and macroscopic properties of solid particles, the analysis of the thermodynamic and kinetic mechanisms of crystal nucleation and growth, as well as and the understanding of the role of large biomolecules in in the kinetic stability of solid crystals.
These elements will allow substantial progress of the current fundamental understanding of crystallization of organic materials and allow the development of formulations that can be used for pharmaceutical, agrochemical and food products that are safer, more sustainable and also more affordable.
Impact on society
The project tackles a major crystal engineering challenge and will generate new knowledge essential for the whole crystallization community. In particular, it will enable the design of biocompatible, safe and sustainable crystals to be used for pharmaceutical and cosmetic formulations, and to develop new products for the food and agriculture industry that are able of controlled release of active ingredients.
In general, the project will contribute to the development of more sustainable manufacturing processes also at the industrial scale and will help the transition of the European Union to a modern and competitive economy, efficiently using resources, as it is necessary to achieve the European Green Deal.
During the first reporting period, albeit with some delays, WP1 and WP2 started. Due to the unavailability of the laboratory space, in this first RP we focused on the modelling work, we took advantage of existing and newly formed collaboration with other research institutions (University of Leeds, Imperial College London, Università di Torino, CNR di Bari) and industrial partners (Nestlé) to access specific laboratory equipment and, finally we performed experiments at large research facilities via a peer-reviewed application process (European, British and Italian synchrotron, ESRF, Diamond and Elettra).
As part of a collaboration with the University of Leeds we explored the crystallization behaviour of natural sugars and collected crystallographic and physical data (e.g. solubility, thermal behaviour). With the University of Leeds and Imperial College London we studied the relationship between crystal structure of a natural flavonoid molecule and its surface properties, using molecular modelling and inverse gas chromatography available at Imperial College. Both studies were published on two different papers in the ACS journal Crystal Growth and Design (details are shown in the publication section of SyGMa) and are part of the tasks envisaged for WP1.
In collaboration with the university of Leeds and the British synchrotron (Diamond Light source), we studied the stabilization mechanisms of cocoa butter crystals based oleofoams that can be used as topical delivery media or for food formulations. The work was published on the ACS journal Langmuir and is part of the project’s WP1 and WP4.
Since the hiring of personnel at Politecnico di Torino and the end of the laboratory refurbishment we started working on WP1, focussing on solid form screening with the recently purchase Crystal16 and CrystalBreeder (equipment specified in the costing plan), particle characterization with chemical force microscopy and formulation characterization with Raman confocal microscopy. We have recently submitted a manuscript on Crystal Growth and Design related to the solid form landscape of quercetin, a natural polyphenol, which was determind as part of a collaboration with CNR Bari and università di Torino.
As part of a collaboration with the University of Leeds we explored the crystallization behaviour of natural sugars and collected crystallographic and physical data (e.g. solubility, thermal behaviour). With the University of Leeds and Imperial College London we studied the relationship between crystal structure of a natural flavonoid molecule and its surface properties, using molecular modelling and inverse gas chromatography available at Imperial College. Both studies were published on two different papers in the ACS journal Crystal Growth and Design (details are shown in the publication section of SyGMa) and are part of the tasks envisaged for WP1.
In collaboration with the university of Leeds and the British synchrotron (Diamond Light source), we studied the stabilization mechanisms of cocoa butter crystals based oleofoams that can be used as topical delivery media or for food formulations. The work was published on the ACS journal Langmuir and is part of the project’s WP1 and WP4.
Since the hiring of personnel at Politecnico di Torino and the end of the laboratory refurbishment we started working on WP1, focussing on solid form screening with the recently purchase Crystal16 and CrystalBreeder (equipment specified in the costing plan), particle characterization with chemical force microscopy and formulation characterization with Raman confocal microscopy. We have recently submitted a manuscript on Crystal Growth and Design related to the solid form landscape of quercetin, a natural polyphenol, which was determind as part of a collaboration with CNR Bari and università di Torino.
We have recently published work using molecular modelling and bulk measurements (inverse gas chromatography, contact angle) to link crystal structure and surface properties of natural crystalline particles. We are progressing this work further with more complex modelling and characterization (e.g. SEM, AFM) and we are hoping to determine a robust methodology to tailor surface properties of particle using crystal engineering. In parallel we are working on the design and characterization of novel Pickering formulations using natural materials, also from agri-food waste. We are planning to apply crystal engineering principle to develop a novel delivery mechanism for food, pharmaceutical and agrochemical formulations.