Prof K Marshall, Prof Aline Miller, Dr D Fischer
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Background
Endometrial cancer and endometriosis are common gynaecological disorders, which arise from the uterine lining. Cancer develops by glandular cell differentiation, whilst implantation and growth of endometrial-like tissue in endometriosis induces a chronic inflammatory reaction causing pain and infertility. Existing surgical and medical interventions are limited by systemic side effects, cost and short-term relief of chronic symptoms (Lindsay et al. 2015). A sophisticated class of hydrogel scaffolds has emerged as a powerful tool for the generation of new biomaterials with adherent gelation properties. Design of these nanostructured peptides can be tailored for potential application to mucosal surfaces for local drug delivery (Tang et al., 2014; Gao et al., 2017).
Hypothesis
Local placement of a drug delivery system at the time of surgery will prevent disease return and reduce the risk of systemic side effects.
Aims
• To develop a hydrogel formulation of promising new and repurposed drugs for targeted delivery to disease sites.
• To examine the therapeutic value of hydrogels using in vitro and in vivo models.
Methods
This project offers a unique experience at leading industrial and academic research sites.
Optimising hydrogel formulations: Manchester BIOGEL’s bespoke peptide-based scaffolds will be tailored for therapeutic application within the pelvic cavity. These hydrogels will be optimised for suitable composition, adhesion and stability with long-acting drug release profiles without appreciable lag or burst effects. Structural and physical properties will be assessed using rheometry, TEM and HPLC-UV.
In vitro and in vivo hydrogel assessment: Prototype drug-loaded and blank hydrogel formulations will initially be evaluated using mouse and human endometrial cells. The effect of drug treatments (novel and known oestrogen suppressors) on cell viability, prostaglandin production and steroidogenesis will be assessed using metabolic response assays, lipidomic analysis and ELISAs. Efficacy of these hydrogel implants will also be examined in vivo with the primary measured end point being a reduction in endometrial lesion or tumour size.
Potential impact
Understanding the design and biological effects of drug-loaded hydrogels should lead to development of a new treatment moiety to prevent recurrence of endometriosis and endometrial cancer. It will provide an exciting opportunity to accelerate the proposed novel hydrogel technology into clinical evaluation to improve the management of these debilitating conditions.
https://www.research.manchester.ac.uk/portal/kay.marshall.html https://www.research.manchester.ac.uk/portal/en/researchers/aline-saiani(85931757-b556-4da2-832b-b3bfa16f976e).html
http://www.polymersandpeptides.co.uk/
https://manchesterbiogel.com/
Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Funding Notes
This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP websitewww.manchester.ac.uk/bbsrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
References
Gao et al. (2017) Biomacromolecules. 18(3): 826-34.
Lindsay et al. (2015) Expert Opin Emerg Drugs. 20(3): 449-61.
Tang et al. (2014) Int J Pharm. 465: 427-435.
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