Prof Jayne Lawrence, Dr Alain Pluen, Dr R Curtis
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Lipid nanoparticles (LNPs), in their various forms - including solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugate and polymer-lipid hybrid nanoparticles - have attracted considerable interest as delivery vehicles for a range of therapeutic candidates. However, regardless of their precise structure, these colloidal particles share common stability issues such as agglomeration/aggregation and sedimentation. Whilst electrostatic, steric or electrosteric stabilization of the nanoparticles can overcome problems with agglomeration/aggregation as well as controlling sedimentation, such strategies frequently take time to develop and contribute to the attrition of the candidates during the development process. To date little or no work has systematically determined nanoparticle stability as a function of nanoparticle composition, stress, time after production, nanoparticle concentration. Additionally, intravenously administered nanoparticles can, depending upon their physico-chemical properties (including their size, shape, charge) result in altered pharmacokinetics and biological performance alter their interaction with blood proteins.
The main aim of the current project is to establish which physical determinants (e.g. storage time, nanoparticle concentration as well as the application of external stresses (e.g. temperature, pH, ionic stress, excipients, plasma components)) destabilise LNPs by the use of an unique combination of low volume sampling techniques and thereby propose rules to facilitate the development process.
The specific objectives are:
- Quantification of the interactions between LNPs as a function of external factors (pH, ionic strength, temperature, excipient(s), blood proteins) with nanoparticle composition using a range of advanced physico-chemical/biophysical tools
- Characterisation of the integrity of the nanoparticles (including their payload) as well as the absence of aggregates using RICS (and SANS) under microfluidic flow
The applicant will be trained to use all necessary techniques for the project e.g. confocal microscopy (RICS), fluorescence correlation spectroscopy, DLS, SANS, SAXS and other additional techniques. He/she will also benefit from the experience of a number of PDRA and PGR student working in the same research area. He/she will also benefit from a placement to our industrial partner, MedImmune, during the programme.
The applicant will follow the Doctoral Academy Training Programme delivered by the Centre for Academic and Researcher Development (CARD). The programme provides key transferable skills in areas such as commercial awareness, academic writing and public engagement. It is meant to equip the PGR student with the tools to progress beyond their research degree into influential positions within academia, industry and consultancy.
The emphasis is on enhancing skills critical to developing early-stage researchers and professionals, whether they relate to effective communication, disseminating research findings and project management skills.
Funding Notes
This is a fully funded studentship that will cover fees and stipend:
Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in (bio)chemical engineering, chemistry, biochemistry, biophysics, pharmaceutical sciences or related subject. A Master’s degree in a relevant subject and/or experience in (bio)chemical engineering, chemistry, biochemistry, biophysics or related subject is desirable. Experience in lipid nanoparticles is desirable. They are also expected to have a strong will to learn different scientific aspects including informatics, nanoparticles and aggregation, formulation, microscopy and image analysis, SAXS, SANS and other relevant techniques e.g. DLS, HPLC.
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