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Characterisation of molecular and cellular processes underpinning nanoparticle distribution

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  • Full or part time
    Dr M Siccardi
    Dr N Liptrott
  • 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

Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Nanomaterials can be applied to favour drug absorption, protect drugs from degradation and to increase the length of time for which drugs are present in the blood circulation and tissues.

The biodistribution of nanoparticles is resulting from a broad variety of processes in different tissues and organs. The various ADME processes are not completely characterised and can substantially different from traditional pharmacological agents such as small molecules. Nanoparticles can reach the systemic distribution through multiple routes, such as oral, transdermal, ocular, nasal, pulmonary and intravenous.

The elimination and clearance of nanoparticles can be regulated by multiple processes including, chemical and enzymatic degradation, renal and biliary elimination. The nanoparticles can firstly undergo degradation in blood, tissues and cells, resulting in the release of the nanoparticle content and/or component. Degradation rate is a relevant variable in the definition of how nanoparticle and their relative content/components can penetrate tissues, complicating the design of technological platform for biomedical applications. There are several in vitro assays that have been well characterised for assessing absorption, distribution, metabolism and excretion (ADME) of pharmacologic agents, in particular small molecules. Many of these have been adapted for use in assessment of nanoparticle ADME. A mechanistic understanding of the molecular and physiological events that define nanoparticle distribution can have beneficial impact on development of novel nanoparticle assessment strategies as well as on characterisation of toxicological risks.
The main project(s) aim will be to integrate different various experimental approaches for the characterization of key nanoparticle distribution processes to support a more rational development of innovative materials for the enhancement of drug distribution across multiple disease areas.

Project Aims:
- Experimental description of key molecular and physiological processes defining nanoparticle distribution
- Integration of in vitro data into a mathematical framework to predict nanomaterial distribution

These studentships are part of a larger European Commision funded initiative, the SAFE-N-MEDTECH consortium, a European H2020 NMBP project involving researchers from the University of Liverpool in addition to 27 other organisations around Europe. The students will join a multidisciplinary team with a wide range of expertise including Pharmacology, Immunology, Materials Chemistry and Computational Modelling and will be expected to fully engage in many aspects of the overall project.

Students with a background in Pharmacology, Pharmacy, Biochemistry, Biology, or Drug Delivery and related subjects are invited to apply for this 36 month fully-funded project. Applicants should send a CV, a letter of motivation and two names of referees who can send letters of recommendation to Dr. Marco Siccardi ([Email Address Removed])

Funding Notes

Fully funded project for 36 months

References

Siccardi M, Rannard S, Owen A. The emerging role of physiologically based pharmacokinetic modelling in solid drug nanoparticle translation. Adv Drug Deliv Rev. 2018 Jun;131:116-121.
Kaminskas, Lisa M., Ben J. Boyd, and Christopher J H Porter. 2011. “Dendrimer Pharmacokinetics: The Effect of Size, Structure and Surface Characteristics on ADME Properties.” Nanomedicine. https://doi.org/10.2217/nnm.11.67.
Vellonen, Kati Sisko, Melina Malinen, Eliisa Mannermaa, Astrid Subrizi, Elisa Toropainen, Yan Ru Lou, Heidi Kidron, Marjo Yliperttula, and Arto Urtti. 2014. “A Critical Assessment of in Vitro Tissue Models for ADME and Drug Delivery.” Journal of Controlled Release. https://doi.org/10.1016/j.jconrel.2014.06.044.
Li M, Zou P, Tyner K, Lee S.Physiologically Based Pharmacokinetic (PBPK) Modeling of Pharmaceutical Nanoparticles. AAPS J. 2017 Jan;19(1):26-42.



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