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  Nanocrystals-in-nanofibres as a promising strategy for the delivery of poorly soluble actives


   School of Pharmacy

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  Dr Alejandro Paredes  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

One of the most challenging issues that the pharmaceutical industry face is poor aqueous solubility of drugs. 90% of candidate molecules within the discovery pipelines face solubility issues, posing significant hurdles to their clinical translation. Moreover, 40% of drugs in the market are also poorly soluble and need to be administered in high doses to reach therapeutic plasma levels. The formulation of drug nanocrystals (NCs) has become one of the most preferred strategies to enhance the absorption of hydrophobic drugs. NCs are nanoparticles made of the pure drug with crystalline properties. Produced using various industrially-available methodologies, NCs have made a significant clinical impact, with >20 products on the market. Since NCs do not contain any carrier material, and are stabilised by a thin stabiliser layer, their drug loading approaches 100%. Given their large specific surface, NCs have an enhanced dissolution rate, saturation solubility and bioahdesion. Initially applied to the delivery of oral medicines (i.e., Rapamune® and Emend®), NCs have been administered via multiple administration routes, including pulmonary, transdermal, ophthalmic, and intramuscular, (i.e., the long-acting products Invega Sustenna® and Cabenuva®). Dr Paredes has worked within the field for >12 years, applying the NCs technology for increasing the oral, intradermal, ocular, and mucosal absorption of poorly soluble drugs. In a major departure from current NCs applications, this project aims to develop a platform consisting of NCs embedded in dissolving nanofibres (NFs) for mucosal administration. The experimental activities will be oriented to the preparation of drug nanocrystals, which will be loaded in nanofibres using electrospinning. The systems will be fully characterised using various techniques, such as dynamic lights scattering, FTIR, XRD, DSC/TGA, and HPLC among others. Dr Paredes’s group attend every year to major pharma conferences and publish papers in internationally recognised journals. The student will be part of an exciting international research group, where they will acquire technical and soft and technical skills key to their professional and personal development.

Applicants should have a 1st or 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Pharmacy, Molecular Biology, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, 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.

Postgraduate Research applicants must have applied to Queen’s, via the Direct Applications Portal.

https://dap.qub.ac.uk/portal/user/u_login.php

Dr Alejandro Paredes: [Email Address Removed]

Dr Paredes’ research profile: https://pure.qub.ac.uk/en/persons/alejandro-paredes

Relevant publications: https://www.sciencedirect.com/science/article/pii/S0168365922001225

https://www.sciencedirect.com/science/article/pii/S0378517323010062

The candidate will be involved in a multidisciplinary project, interacting with other students and experts in complementary research fields. The student will receive training-through-research in different formulation techniques and processes related to the production of solid drug nanoparticles (nanocrystals) by top-down and bottom-up approaches, with an emphasis on media milling, nanoprecipitation, freeze-drying and spray-drying. Nanoparticle characterisation will cover dynamic light scattering (size and distribution), electronic microscopy (morphology and size) and electrophoretic light scattering (surface charge). The student will perform release experiments using dialysis membranes and Franz cells. Moreover, they will be encouraged to obtain a UK Animal Handling License, which will allow them to perform pharmacokinetics and biodistribution experiments in rats. The student will receive comprehensive hands-on training in high-performance liquid chromatography (HPLC) for the quantification of drugs in different biological and non-biological samples. The student will learn to statistically process and present data to scientific audiences and also to communicate information to a broader public, in written form and orally. 

Improving patients’ quality of life by the development of novel optimized therapies for difficult-to-treat diseases. Interaction with private partners from the pharmaceutical industry will allow the commercial development of nanocrystal-based products. The PhD candidate will improve their CV by receiving training-through-research and presenting their work at major international conferences, as well as publishing scientific papers in high-impact journals. 


Chemistry (6) Medicine (26)

References

Nanocrystals, nanotechnology, drug delivery, pharmaceutics
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 About the Project