Targeted delivery of appetite suppressing peptide for obesity therapy

Obesity is a global epidemic with 500 million adults affected and 1 billion adults classified as overweight (WHO). Currently, the most effective treatment for obesity is gastric surgery, which is invasive, expensive and carries several risks and side-effects. Recent research has therefore focused on gaining a better understanding of the relationship between appetite regulation and obesity. Peptide YY (PYY) is a naturally occurring hormone that plays a pivotal role in regulating appetite and energy balance. PYY is thus considered a promising candidate for obesity therapy. However, several aspects, such as the site of conversion of PYY to active PYY3-36 and the mechanisms regulating this are poorly understood, and therefore no pharmaceutical product is available for the treatment of obesity based on PYY. Our recent research demonstrated that PYY gene is expressed in the human gut epithelial cell line Caco-2, and we hypothesise that intestinal epithelial cells play a crucial role in appetite sensing and regulation. Building on this background, the initial aims will be to study the dynamics of conversion of PYY to PYY3-36 and its secretion, and clarify the underlying mechanisms. Based on our findings we will proceed to the formulation phase of the project wherein we will use novel in-house polymer synthesis and drug delivery approaches to formulate PYY loaded oral nanocarrier systems designed to target the gut and replicate the endogenous release profile of plasma PYY3-36. The applicant would benefit from working in a multidisciplinary project and being trained in an array of techniques: e.g. in-vitro techniques such as Transwell® co-culture and cell/molecular biology techniques such as immunoassays, immunoblotting, qPCR, and confocal microscopy. The candidate will also gain training in state of the art formulation and characterisation techniques such as nano-spray drying, HPLC, DSC and TEM at the UCL School of Pharmacy. The candidate will take part in career development workshops and gain training experience in several partner laboratories in the UK and overseas. The candidate will also benefit from comprehensive career development opportunities via the UoW doctoral research development programme provided b the graduate school and faculty (http://tinyurl.com/k6k2y6v).The research is envisaged to result in high impact publications in journals such as PNAS and FASEB. Research outcomes will also be disseminated at conferences of relevant scientific societies (e.g. Society for Endocrinology) and ENDO of which the candidate would gain membership. This studentship will therefore provide the PhD candidate an opportunity to start a career in a topical, interdisciplinary project that has the potential to have significant clinical relevance in the area of obesity therapeutics and nanomedicine.