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Accelerated Synthesis of Branched Polymer Drug Delivery Systems

An accelerated synthetic route to novel branched polymer drug delivery conjugates will be tested. The polymers will be analysed via chromatographic and spectroscopic techniques.

Department: Chemistry

Supervised by: Wayne Hayes

The Placement Project

Conjugation of highly potent but frequently insoluble anticancer drugs to polymers to improve the therapeutic efficacy has been adopted successfully in modern chemotherapy. Dendrimers offer great promise as drug delivery systems on account of their branched structure, multiple chain ends and excellent aqueous solubility. However, synthesising dendrimers is difficult - complex multi-step routes are required which financially and practically challenges scale up to enable transfer from laboratory trials to the clinic. This project will test an accelerated synthetic route to dendritic polyethylene glycol-based materials and model conjugates. Short reaction times and simple purification methods will be targeted. Robust and scalable ester bond formation will be used to enable product purification via simple extraction chemistries. Conjugation of drug mimics onto the dendritic polymer to afford model drug delivery systems will be achieved via highly efficient coupling reagents. The model dendritic drug delivery systems will be characterised using chromatographic and spectroscopic techniques. This project will allow the student to become familiar with aspects of research in a synthetic polymer group. The applicant will design, synthesise and characterise a small series of dendritic polymers and model drug conjugates as well as assessing their aqueous solubility. With appropriate supervision from Professor Hayes and his research group, the student will be able to make rapid progress, ensuring the project through from conception to application over a short six week period, enabling them to gain valuable exposure to all aspects of synthetic polymer chemistry and the polymer drug delivery programme in the Hayes group.

Tasks

The student will spend approximately 4 weeks on the design, synthesis and characterisation of novel polymers. The synthetic component will require the use of all standard laboratory equipment including hotplate-stirrers, glassware and chromatography columns. During the remainder of the placement, the student will characterise the resulting polymers using the full suite of modern instruments available in the Chemical Analysis Facility, such as nuclear magnetic resonance, mass spectrometry and infra-red spectroscopy. The solubility characteristics of the polymers will be probed via Ultraviolet/visible or fluorescence spectroscopy which will also be carried out in the Chemical Analysis Facility.

Skills, knowledge and experience required

The successful applicant should have a working knowledge of basic laboratory skills including synthetic organic chemistry procedures and routine chemical analysis such as NMR, IR and MS. They should also be competent in chemical database searching (Scifinder, Web of Knowledge) and have a working knowledge of chemical structure drawing software (such as Chemdraw).

Skills which will be developed during the placement

The student will be exposed to all aspects of modern synthetic polymer chemistry research. They will plan and complete new reactions during which time they will acquire knowledge in how to isolate and characterise novel polymers. This will require extensive, hands-on use of cutting-edge analytical equipment such as that found in the Chemical Analysis Facility on campus. The remainder of the time will be spent analysing and evaluating the solubility characteristics of the new polymers ascertain their viability for use as drug delivery systems. Alongside these tasks, the student will write concise weekly progress reports which will be combined to form a thesis-style summary of their achievements during the placement. This will require use of chemical drawing packages (Chemdraw) in addition to referencing databases and programs (Scifinder, Endnote). The report will form the basis of potential publications for which the student will receive authorship credit. Finally, the student will write and deliver a 15 minute lecture on their research to the Hayes research group at the end of their placement, gaining key presentation skills in Powerpoint and lecturing techniques. The student will thus develop a portfolio of valuable practical and theoretical knowledge in organic chemistry but also highly transferable skills for employment outside of the chemical industry.

Place of Work

The synthetic component of the work will be carried out in laboratory 204 in the Chemistry building. Analysis of the polymers will be completed in the Chemical Analysis Facility in the Chemistry and Pharmacy building.

Hours of Work

37

Approximate Start and End Dates (not fixed)

Monday 07 July 2014 - Friday 15 August 2014

How to Apply

The student should apply by sending a CV and covering letter to Professor Hayes. Interviews will be held to select the best candidate – the interviews will feature a technical component whereby the organic chemistry knowledge and ability of the candidates to solve synthetic problems will be assessed. Feedback on the interviews will be given to each candidate to aid their professional development.


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