Formulation of PHMB-based nanoparticles for targeted killing of zoonotic fungi

Dr Liam Good. Department: Pathology and Pathogen Biology, Royal Veterinary College
Dr. David Cook, Dr. John Ridden, Blueberry Therapeutics Ltd

Project Description

HYPOTHESIS: existing antifungal drugs can be potentiated by targeted delivery into fungi via nanoparticle formulation.

THE PROBLEM: It is difficult to develop much-needed new anti-fungal agents. The challenges include stringent fungal cell barriers (limiting drug access to the pathogenic target) and biochemical similarities with host cells (producing undesirable safety liabilities via “drug cross-talk”).

OUR IDEA: Nanoparticles can target fungal cells and promote cell entry, and thus improve pathogen killing and safety.

THE PARTNERSHIP: The partnership involves academic labs (Royal Veterinary College, UCL-Centre for Nanotechnology and Regenerative Medicine & UCL-School of Pharmacy), and an SME (Blueberry Therapeutics Ltd). Recently, the RVC lab discovered that PHMB is able to enter a wide range of cells, including fungi, and the polymer can be used to deliver drugs into a range of cells (WO/2013/054123, Firdessa et al. 2015 PLoS NTD; Kamaruzzaman et al. 2016 JAC; Chindera et al. 2016, Nature, Sci. Rep). The UCL lab currently works with polymers to generate nanoparticles for drug delivery. The UCL-SoP scietists are experts in skin science. BBT has broad experience in drug development and a strategic focus on reformulating antifungal compounds to improve cell and tissue delivery for clinical development. The partnership connects microbiology, nanotechnology, polymer chemistry, engineering, skin science and drug development.

OBJECTIVES

  • Determine the antifungal mechanism(s) of action of PHMB against Candida and Malessezia species.
  • Design and construct nanoparticles using small molecule antifungals and polymer. The polymer has a high capacity for electrostatic, hydrophobic and H-bonding interactions.
  • Measure antifungal activities. Minimum inhibitory and cidal concentrations will be determined.
  • Assess mechanism(s) of cell uptake. Uptake mechanism(s) into fungi will be evaluated using microscopy, uptake pathway inhibitors and biophysical methods.
  • Measure host cell impact. Proliferation or stress will be measured using cultured keratinocytes, lung epithelial cells and ex vivo human skin.
  • Assess scale-up feasibility. The effects of scale-up on encapsulation ratio, particle size and particle uniformity will be determined, along with consideration of regulatory aspects.



This exciting project builds on existing data and expertise and will develop nanoformulations that can improve human/animal life quality and help to reduce healthcare and animal husbandry expenditures. The project is important, because fungi threaten the extinction of hundreds of species, and fungal infections of the skin was the 4th most common disease in 2010, affecting 984 million people. This project will establish a clear pathway from the design and manufacture of antifungal nanoparticles. The basic strategies and safety assessments developed will be relevant to human/animal health – aligning with OneHealth.

Training

The student will work with established experts in microbiology (Department of Pathology and Pathogen Biology, RVC), nanomaterials and bioprocessing (Centre of Nanotechnology and Regenerative Medicine, UCL-CNRM), skin science (School of Pharmacy, UCL-SoP), and drug development (Blueberry Therapeutics, BBT). This project offers an excellent opportunity for a researcher to be involved in sophisticated nanoengineering and the evaluation of antifungal formulations for drug development with a pre-clinical/clinical perspective. Blueberry Therapeutics Ltd is located within the BioHub, at Alderley Park, one of the UK’s largest Biotech incubators.

Application

Applicants should have an interest in working on projects that combine nanotechnology with microbiology to improve infection control. Prior experience with nanotechnology, microbiology, cell biology, microscopy, pharmaceutical sciences or closely related areas would be an advantage. Also, the candidate must be interested to learn from both academic and industrial laboratories within a drug development project. Strong inter-personal and communication skills are required.

Applicants must hold, or be expected to achieve, a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject. Interested applicants are encouraged to contact Liam Good (lgood@rvc.ac.uk) in advance of the deadline, 20th January 2017 at 5pm.


To apply you will need to send the following documents in a single email to: LIDo.Admissions@ucl.ac.uk. All documents must be submitted in unprotected PDF format.


  • Completed Application Form (Sections A and B) including details of two Academic References
  • The disability and ethnic origin monitoring form
  • Official Final Transcripts from Completed Programmes of Study
  • Official Interim Transcripts from On-going Programmes of Study
  • English Language Qualification (if required, please see below)
  • Academic CV
  • Copy of Passport

Please click the relevant links below to download a zipped folder of application documents in your preferred format.
Application Pack (Word).zip
Application Pack (PDF).zip