Microfluidic Encapsulation of biologics into Nanomedicines

Progress in drug design has led to the development of new peptides, proteins, and drug molecules. However, the limited ability to deliver selectively these molecules at well-defined dosing regimens and without invoking drug-resistance remains a significant challenge. Another challenging aspect of some smaller sized biologics is the clearance rate.  Certain modifications are required to enable effective residency time in the body. Therefore, the development of effective therapies relies on the development of effective carriers that can mitigate these challenges.

Historically, lipid encapsulation of an API has led to the protection of bio-sensitive APIs, such as biologics. Evidence of this is well documented in literature. The use of carriers such as liposomes, prevents a variety of proteases from early degradation of the protein-based molecules. The initial step of encapsulation within a liposome also provides the opportunity for future membrane modification, for example with PEGylated phospholipids. This would open the door to a higher capacity for targeted delivery or altering pharmacokinetic parameters such as residence time.

The confined volumetric environment provided by the Microfluidic (MF) environment coerces the self-assembly process during encapsulation to be performed in a controlled and reproducible manner. MFs can be considered as a far greener process compared to other methods currently used by companies, not only by the reduced number of materials, but also the time (and hence subsequent energy exposure) taken for formulation. The system allows the production of encapsulated NPs with predictable sizes and PDI with the need for minimal post processing. This aspect means that a pharmacopoeia grade formulation can be produced in a short and economically viable way.

The aim of this Ph.D. project, which includes formulation, scalability of the MF platform, computational modelling, in vitro and (potentially) in vivo studies, is the development of formulations for the successful delivery of biologics, which could be subject to extensive metabolism or clearance post-administration, which highlights the need for alternative formulation suing MFs. The goal is to develop and optimise a method to successfully delivering a range of biopharmaceutical molecules.

Applicants should have a 1^st or 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biomedical Sciences, Chemistry, Chemical Engineering, or a closely related discipline. Students who have a 2.2 honours degree and a Master’s degree may also be considered, but the school reserves the right to shortlist for interview only those applicants who have demonstrated high academic attainment to date.

The successful applicant will be integrated into QUB research groups of experienced researchers with access to world-leading facilities and will work in close collaboration with an industrial sponsor. The successful candidate will also have the opportunity to spend time to the industrial sponsor and being exposed to industrial view on drug development, attend conferences, mini courses & workshops for further development.

The techniques that will be used during the project cover a wide-range and include: microfluidics, Atomic force microscopy (AFM), Differential Scanning Calorimetry (DSC), Thermal Gravimetric Analysis (TGA), Fourier-transform Infrared (FTIR) Spectroscopy, Scanning Electron Microscope (SEM), Rheology, Nuclear Magnetic Resonance (NMR), and In Vitro Release Studies. Transferrable skill training will also include research management, personal effectiveness, communication skills, networking, team working and career management. 

The PhD student would be encouraged to engage in a variety of impact activities, disseminate the research project findings through public talks, and participate in QUB showcase events. Examples of impact activities includes: Blogs or web articles, Magazine articles, public lectures, School visits, oral & poster Presentations (at local, national and international conferences), and Publication of scientific papers in peer reviewed journals.