Protein-based therapeutics are an important class of medicine with significant value for the treatment of many relevant disorders such as cancers, inflammation, and exposure to infectious diseases. Despite their advantages, proteins are limited by short biological half-lives and typically require frequent dosing via injection. This can lead to reduced patient compliance and increased potential for side-effects, hampering therapeutic efficacy. Providing sustained protein release is therefore key to efficient and safe therapy. However, developing drug delivery systems which ensure long-term protein release and stability remains a significant challenge.
The proposed PhD project will focus on developing lipid-based implants via melt processing for sustained protein release. Lipid-based systems are biodegradable, biocompatible and have been successfully used to demonstrate controlled protein release. Melt processing is a versatile manufacturing technology and a promising encapsulation method for biomacromolecules. The scientific approach of this project is to develop protein-encapsulated lipid-implants for sustained release while maintaining protein structural stability and bioactivity. To do so, the impact of melt processing on protein release and stability of the protein drug will be investigated. Protein stability will be safeguarded via covalent and non-covalent polymer-based strategies (e.g., PEGylation) and polymorphic changes will be correlated with protein release profiles. The developed lipid-based implants will be characterized and biologically activity evaluated in vitro and in vivo. The successful candidate will be part of a highly interdisciplinary project and have the opportunity to learn about lipid formulation, protein formulation, bioconjugation, biological testing and continuous manufacturing.