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Nasal Delivery of Peptide Nanofibers for Acute Ischaemic Stroke

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  • Full or part time
    Dr A Lalatsa
    Prof A Butt
    Dr A Bucchi
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Applications are invited for a fully-funded three year PhD to commence in October 2019.

The PhD will be based in the School of Pharmacy and Biomedical Sciences and will be supervised by Dr Aikaterini Lalatsa, Professor Arthur Butt and Dr Andrea Bucchi.

Project description

Stroke is a brain attack caused by the blood supply to the brain being cut resulting in damage and death of brain cells. Every two seconds, someone in the world will suffer from a stroke with stroke being the fourth single cause of death in the UK. Two thirds of stroke survivors will leave the hospital with a disability (weakness in limbs, problems with speech, reading, writing, eyesight, memory, thinking and swallowing) costing the NHS 1.7 billion annually in treatment and rehabilitation.

Although restoring blood flow as quickly as possible is critical, the use of clot-dissolving agents such as tissue plasminogen activator (tPA) is limited by the risk of haemorrhagic events and delayed hospitalisation, thus only 3% of the patients can be treated within the 4.5 hours window during which the tPA, the only available treatment, is effective. Thus developing novel treatments that ideally are non-invasive and able to be administered by paramedics and with reduced risk of haemorrhage are needed to minimise the severity of the ischaemic attach and limit the morbidity and mortality of stroke.

Recent research has demonstrated that short neuropeptides belonging to the Angiotensin family can exert cerebrotective effects in ischaemic stroke and when administered intracerebrally they can reduce the infarct size and prolong survival. However, the inability of these peptides to cross the blood-brain barrier in adequate quantities and their very short biological half-lives (below 2 minutes) are key challenges limiting their translation into non-invasive therapies for stroke.

Our group has recently shown that lipidising neuropeptides can result in peptide amphiphiles able to self-assemble in long-axial nanofibers (Leite et al 2015 Curr Top Med Chem 15 (22): 2277-2289) that possess excellent biological stability, are able to cross the blood-brain barrier and activate receptors within the brain parenchyma eliciting a pharmacodynamic response via an intravenous (Lalatsa 2015 J Control Release 197:87-96, Leite 2017 ACS Nano In preparation) but also via an intranasal route (PCT/GB2014/ 053254, Godfrey, L et al 2017 Nanoparticulate peptide intranasal delivery exclusively to the brain to produce centrally mediated, tolerance free analgesia. ACS Nano Submitted). This projects aims to develop a non-invasive peptide based nanomedicine presented as microparticles appropriate for nasal delivery for the treatment of stroke.

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 endocrine targets into non-invasive targeted delivery strategies for stroke. The successful candidate will gain experience and receive training in design of lipidised peptide analogues in silico, solid-phase peptide synthesis and characterisation, physicochemical and morphological characterisation of self-assembled nanofibers , preparation and characterisation of nano in micro particles for nasal delivery, stability of peptide nanofibers in plasma, brain, liver and nasal mucosa homogenates, studies on brain slices exposed to oxygen-glucose deprivation (OGD) coupled with pharmacological activation or blockade of targeted receptors, measurement of reactive oxygen species, computational flow dynamics and permeability studies across an in vitro BBB model, and receptor binding studies using single molecular force spectroscopy (in collaboration with University of Linz. Depending on the success of the project in vivo pharmacokinetic (LC-MS) and pharmacodynamics


How to Apply

We’d encourage you to contact Dr Aikaterini Lalatsa ([Email Address Removed]) to discuss your interest before you apply, quoting the project code.

When you are ready to apply, you can use our online application form and select ‘Biomedical, Biomolecular and Pharmacy’ as the subject area. 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 PHBM4810219 when applying.

Funding Notes

The bursary is available to UK and EU students only and covers tuition fees and an annual maintenance grant in line with the RCUK rate (£14,777 for 2018/19) for three years.



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