Developing a hydrogel-based localised therapy for endometriosis

The World Endometriosis Research Foundation estimates that over 176 million women worldwide
suffer from endometriosis. It is typically a peritoneal-based condition where implantation and
growth of endometrial-like tissue induces a chronic inflammatory reaction causing pain and
infertility. Existing surgical and medical interventions are limited by lack of understanding of the
disease, systemic side effects, cost and short-term relief of chronic symptoms. A sophisticated class
of hydrogel scaffolds has emerged as a powerful tool for the generation of new biomaterials with
adherent gelation properties. Design of these nanostructured peptides can be tailored for potential
application to mucosal surfaces for local drug delivery.
Hypothesis
Local placement of a pelvic drug delivery system at the time of surgery will retard disease return,
whilst maintaining the patient's fertility.
Aims
To develop a hydrogel formulation of promising new and repurposed therapeutic agents for
targeted delivery to endometriosis sites.
To examine the in vitro and in vivo effect of drug treatments using a validated model of
endometriosis.
Methods
This project will involve a multi-faceted approach, offering unique experience at leading industrial
and academic research sites.
Optimising hydrogel formulations: Our bespoke peptide-based scaffolds will be tailored for therapeutic application within the pelvic cavity. These hydrogels will be optimised for suitable
composition, adhesion and stability with long-acting drug release profiles without appreciable lag or
burst effects. Structural and physical properties will be assessed using transmission electron
microscopy (TEM), rheology measurements and high performance liquid chromatography with UV
detection (HPLC-UV).
In vitro and in vivo hydrogel assessment: Prototype drug-loaded and blank hydrogel formulations will
initially be evaluated using mouse and human endometrial cells. The effect of drug treatments (novel
and known oestrogen suppressors) on cell viability, prostaglandin production and steroidogenesis
will be assessed using metabolic response assays, lipidomic analysis and ELISAs. The therapeutic
value of these hydrogel implants will also be examined in vivo using our clinically valid mouse model
of endometriosis. The primary measured end point will be reduction in endometrial lesion size.
Potential outcomes/ impact
Understanding the design and biological effects of drug-loaded hydrogels should lead to
development of a new treatment moiety to prevent recurrence of endometriosis. It will provide an
exciting opportunity to accelerate the proposed novel hydrogel technology into clinical evaluation to
improve the management of this debilitating disorder.