PhD: Formulation optimisation and preclinical evaluation of oral-targeted nanoformulations of therapeutics for the treatment of IBD
The aim of this project is to optimise these nanoformulations and examine their efficacy in a preclinical colitis mouse model. As part of this project, nanoformulations will be optimised for Infliximab loading, drug release and stability over time.
- Principle investigator(s) Dr Zeibun Ramtoola, Prof. Brian Kirby
- Research theme Chemistry and Pharmaceutical Sciences, Immunity Infection and Inflammation
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects the gastrointestinal tract (GIT) of the patient and comprises of Crohn’s disease (CD) and ulcerative colitis (UC). In CD, inflammation can occur in any part of the GIT, whereas in UC, ulceration is usually limited to the lower part of the GIT, namely small intestine, colon and rectum.
IBD patients suffer a wide variety of symptoms including abdominal pain, diarrheoa, rectal bleeding, and anaemia, negatively impacting their quality of life. Current treatment comprises the administration of small molecule therapeutics such as 5‐aminosalicylic acid, corticosteroids, immunosuppressants including cyclosporine and the anti-TNFα monoclonal antibodies (mAbs) such as infliximab. While conventional small molecules provide relief from IBD symptoms and maintain symptomatic remission, disease progression ultimately leads to colectomy.
Anti-TNFα mAbs is recognized to promote GI mucosal healing, a key goal of IBD treatment, as this reduces the need for surgery. A major disadvantage of mAb therapy, however, is the resulting severe adverse effects such as leucopenia, serious infection and increased risk of malignancy due to their systemic administration at high doses. The development of novel drug delivery strategies of anti-TNFα therapeutics that can enhance their efficacy and reduce their side effects is therefore a priority for the treatment of IBD. Budesonide nanoparticles administered orally in a colitis mouse model, were shown to be preferentially to be taken up by the inflamed GIT cells, resulting in enhanced efficacy and reduced side effects . We designed novel stable nanoformulations of infliximab and showed their enhanced cell uptake in an in‐vitro intestinal inflamed cell model, which resulted in reduced inflammation and recovery of the epithelial barrier function.
Optimised nanoformulations will be screened in an inflamed epithelial cell model and subsequently evaluated in the colitis mouse model for their ability to target inflamed tissues, to reduce inflammation and promote healing. Such a targeted strategy may provide increased efficacy, lower dose required, resulting in reduced systemic side effects and enhanced benefit to risk ratio of anti-TNFα mAbs.
Tenure: Four years
- Upper second class (2.1) honours degree (or equivalent) in pharmacy, pharmacology or other biological sciences
Desirable candidate specifications include:
- In-vitro cell culture techniques desirable, but not essential
There is an open rolling registration for this position.
Please apply with an up-to-date CV, a 500-word statement outlining your interest in and suitability for the position, and contact details of two referees to firstname.lastname@example.org.
Successful candidates will be able to attend a virtual interview if they wish.
The position will begin on 1 October 2020.