A crystal engineering approach for novel Pickering formulations with controlled release properties

This PhD project aims at developing novel sustainable, biocompatible multiphase formulations (e.g., emulsions, foams) for the controlled release of active ingredients, applying a unique crystal engineering approach. Multiphase formulations are used for pharmaceutical and agrochemical applications as carriers for hydrophobic active ingredients. Since these colloidal systems are often thermodynamically unstable, surfactants or solid particles (Pickering stabilizers) are added to increase kinetic stability. Solid particles provide better stability and enable tuning of stabilizing properties via control of particle size, shape and wettability. Most Pickering stabilizers used for pharmaceutical and agrochemical formulations are synthetic polymers, whose wettability is tailored via chemical manipulation of their molecular structure. These compounds present poor biodegradability and might be harmful to humans; therefore, the use of natural particles such as cellulosic materials or flavonoids would be a valuable alternative. In order to preserve their natural state, these materials should not be altered chemically, but a crystal engineering approach can be used to optimize their stabilizing efficiency. This project will develop such approach and apply it to the design of novel sustainable, biocompatible, and stimuli responsive multiphase formulations for the encapsulation and controlled release of active ingredients.
The project will be mainly experimental but it will also include a molecular modelling component. Experimental work will involve the controlled growth and characterization of Pickering crystals using a wide range of techniques including electron microscopy, X-ray diffraction and photoelectron spectroscopy (surface chemistry characterization), polarized and Raman microscopy. The thermodynamic stability of different crystal structures will be assessed with dynamic vapour sorption, hot stage microscopy and differential scanning calorimetry while the crystal behaviour at the interface of multiphase formulations will be characterized via confocal microscopy and x-ray radiography/tomography. Multiphase systems prepared will be characterized using light scattering, confocal and electron microscopy techniques and the kinetics of release will be measured using adsorption behaviour in a range of substrates and fluorescence techniques. Molecular modelling using the Attachment Energy model will be performed in order to understand how molecular interactions affect crystal surface chemistry.