PostDoc Fellow - A novel extended release and liver protecting c
AstraZeneca Göteborg / Apotekarjobb / Mölndal
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hela Sverige Long title: A novel extended release and liver protecting coating of drug nanocrystals provides prolonged exposure of drug following IV administration.
Pharmaceutical Sciences IMED.
Pharmaceutical Sciences focusses on the intelligent design of medicines and delivery systems. The department has three priority areas - early chemical development, early product development and advanced drug delivery - supporting synthesis, formulation and delivery of the IMED's portfolio across the main therapy areas, from early discovery to Phase llB clinical trials.
Due to robustness and extremely high drug load (>95% active drug in formulation), stabilized nanocrystal formulations are increasingly popular in the pharma industry. The approach is mainly used to improve dissolution rate and drug exposure for oral administration. However, the most promising application is for parental administration where the goal with a nanocrystal formulation up to now only is to mimic the pharmacokinetic (PK)-profile of a solution (in most cases the only way to handle and administer a poorly soluble compound). Our aim in the present project is to achieve prolonged exposure in blood by development of a novel extremely thin coating for nanocrystals using for instance lipid mixtures. An extended release after intravenous (IV) administration could allow compounds with less optimal PK-profiles to be developed, it could provide better safety windows for drugs that need to be IV-administered, it would be a necessity for truly efficacious (local) drug targeting approaches, reduce dose and extend efficacy over time. During the development of nanocrystals, an in vitro assay, to investigate the surface of the particles is of outmost importance. Using quartz crystal microbalance with dissipation (QCM-D) monitoring both mass adsorption and the thickness of the adsorbed layer can be estimated on macroscopic surfaces mimicking the drug crystals. The technique is not commonly used within the pharmaceutical industry today. The approach is ideal for evaluating the mixtures of lipids (to sustain dissolution) and PEGylated lipids (to avoid liver uptake) necessary to achieve optimal in vivo effect. The link between the surface of nanocrystals and the macroscopic surface will be investigated and surface will be optimized to mimic the surfaces of the nanocrystals. In summary:
1, Novel (for instance) lipid mixtures will be investigated and evaluated using QCM-D
2, The most promising mixtures will be applied on nanocrystals
3, In vitro and in vivo characterization of the prepared nanocrystals will be performed
You are not supposed to work with the in vivo studies.
For a deeper understanding of the project, the references (and references therein) below could be of interest:
Rydberg et al 2016, Probing adsorption of DSPE-PEG2000 and DSPE-PEG5000 to the surface of felodipine and griseofulvin nanocrystals. Int. J. Pharm. 510, 232-239.
Sigfridsson et al. 2017, Nanocrystal formulations of a poorly soluble drug. 1. In vitro characterization of stability, stabilizer adsorption and uptake in liver cells. Int. J. Pharm. 518, 29-40.
Sigfridsson et al. 2017, Nanocrystal formulations of a poorly soluble drug. 2. Evaluation of nanocrystal liver uptake and distribution after intravenous administration to mice. Int. J. Pharm. 524, 248-256.
We're currently looking for talented scientists to join our innovative academic-style Postdoc. From our centre in Gothenburg Sweden, you'll be in a global pharmaceutical environment, contributing to live projects right from the start. You'll take part in a comprehensive training programme, including a focus on drug discovery and development, given access to our existing Postdoctoral research, and encouraged to pursue your own independent research in cutting edge laboratories. It's a newly expanding programme spanning a range of therapeutic areas across a wide range of disciplines.
Education and ExperienceRequired:
Essential:
You should hold a Ph.D. in physical chemistry or similar, with understanding of surface chemistry.
Desirable:
Practical experience of QCM-D or related techniques of value for the project is a merit. Experience specifically of stabilized drug nanocrystals is an advantage.
Skills and Capabilities required:
Theoretical and/or practical experience of nanoparticles is required. The successful candidate is supposed to spend a significant amount of time in the laboratory collecting raw data, analyze and evaluate/interpret the data i.e. documented practical skill and experience from laboratory work is required. Excellent English, both written and spoken. The candidate is supposed to be the driver and responsible author in preparing and writing posters and external publications.
This is a 3 year programme. 2 years will be a Fixed Term Contract, with a 1 year extension which will be merit based. The role will be based at the Gothenburg site with a competitive salary on offer
you share our passion for scientific excellence, find out more at;
https://careers.astrazeneca.com/students/programmes/post-doctoral-programmesAbout AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines for some of the world's most serious diseases. But we're more than one of the world's leading pharmaceutical companies. At AstraZeneca, we're proud to have a unique workplace culture that inspires innovation and collaboration. Here, employees are empowered to express diverse perspectives - and are made to feel valued, energised and rewarded for their ideas and creativity.
What's more, you'll have the support of a leading academic advisor, who'll provide you with the guidance and knowledge you need to develop your career. This is an exciting area that hasn't been explored to its full potential, making this an opportunity to make a real difference to the future of medical science.
Publiceringsdatum2018-04-12Så ansöker duSista dag att ansöka är 2018-05-12
Klicka på denna länk för att göra din ansökanFöretagAstraZeneca Göteborg
AdressAstraZeneca Göteborg
Pepparedsleden 1
43183 MÖLNDAL
KontorsadressPepparedsleden 1
Jobbnummer 4079164
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