Overcoming the barriers to brain delivery; bioengineering 3D printed microfluidic chips to continuous manufacture targeted nanoparticles and elucidate their nose to brain permeability
Fully funded (UK/EU/International students)
School of Pharmacy and Biomedical Sciences
23 February 2020
This PhD studentship is one of six PhD studentships funded by the University of Portsmouth in the area of biomaterials and bioengineering. These studentships will support the University’s strategic plan engaging with clinicians working in Portsmouth Hospital Trust to solve real-life medical problems. The successful applicants would be part of a cross-faculty research cluster in medical technologies.
This programme of research involves several Schools based in the Faculty of Science and Health and the Faculty of Technology. The vision of the cluster is to train a cohort of PhD students who contribute to the academic environment, some of whom would be expected to develop academic careers in this expanding area whilst others would be employed in the growing international medical technologies industry.
Training would be enhanced by extended visits to other institutions involved in similar research and by visits to hospitals to meet with clinicians involved in the research projects.
The scholarship covers tuition fees and an annual maintenance grant of £15,009 (UKRI 2019/20 rate) for three years. Scholarship recipients will also receive up to £3,000 for research project cost/consumables during the duration of the programme.
The work on this project will involve:
- Continuous microfluidic fabrication of nano-in-micro loaded formulations optimised for targeted nose-to-brain delivery.
- Develop mathematical models for the continuous fabrication of nano-in-micro formulations and flow of nanoparticulate formulations within microfluidic organ-on-chips.
- Design and manufacture organs-on-chips models for the nasal epithelial cells and 3D blood-brain barrier validating the permeability of known transport markers and assessing the permeability of brain therapeutics and nanomedicines.
Treatment of brain diseases (neurodegenerative disorders, stroke, pain etc) and tumours is hampered by the inability of majority of developed preclinically medicines to cross the blood-brain barrier and reach the target cells within the brain in adequate levels to elicit a therapeutic response (Lalatsa, A et al (2014)Mol Pharm 11 (4): 1081-93).
Preclinical development of brain therapeutics commonly involves testing of potential therapies in in vitro cell cultures, but developmental therapeutic programmes do not advance without results from animal models (pharmacokinetic and pharmacodynamics studies).
Nose-to-brain delivery have emerged as a viable pathway for transport of drugs/biomacromolecules across the blood-brain barrier and remains the only non-invasive delivery strategy for efficient brain delivery of therapeutics and biotherapeutics especially when chronic administration is necessary (e.g. Alzheimer’s disease, Parkinson’s disease, Stroke) [Uchegbu, IF, Schätzlein, AG, Lalatsa, A, Godfrey L, Ianitelli, A. Delivery of Drugs WO/2015/063510, Published].
However, in vivo permeability assays are needed to understand permeability following nose-to-brain delivery prior translation into human studies even though animal models show significant differences to human studies.
This project aims to design and engineer microfluidic chips and mathematical models for the continuous manufacture of brain targeted nanoparticles and microfluidic human organs-on-chips models able to elucidate nose-to-brain permeability of therapies ideally replacing the need for preclinical studies and accelerating the translation of brain therapeutics and nanomedicines.
This is a multi-disciplinary project between the School of Pharmacy and School of Engineering at University of Portsmouth. The project presents an opportunity to work at the interface between bionanomaterial engineering, cellular and molecular medicine and drug delivery aiming to address challenges in relation to permeation across the BBB and translation of novel nose-to-brain nanomedicines into non-invasive targeted delivery strategies for brain diseases.
The successful candidate will gain experience and receive training in the areas of additive manufacturing, 3D printing and bioprinting, computational flow dynamics, biomaterials, cell biology, neuroscience, an all human 3D in vitro BBB model, and permeability studies.
In addition to exceptional facilities (e.g. 3D printer and bioprinter, live cell imaging, TIRF microscopy, electron, scanning and atomic force microscopy, laser confocal microscopy, flow cytometry, electrical Cell Substrate Impedence Sensing system (ECIS) system and CellZscope) and comprehensive training at the University, the student will also gain added value by having the opportunity to directly interact with our industrial partners and enhance specific and transferable skills.
You will need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in biomedical engineering, chemical engineering, materials science, nanotechnology, pharmacy and pharmaceutical sciences. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.
The successful applicant will be a talented researcher with an enthusiasm for biomedical engineering, chemical engineering, biomaterials, materials science, nanotechnology, pharmacy/pharmaceutics
How to apply
We’d encourage you to contact Dr Aikaterini Lalatsa at firstname.lastname@example.org to discuss your interest before you apply, quoting the project code/title.
When you are ready to apply, you can use our online application form. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV.
Our ‘How to Apply’ page offers further guidance on the PhD application process.
If you want to be considered for this funded PhD opportunity you must quote project code PHBM4841020 when applying.