Bioengineering a mucoadhesive composite for the delivery of chemotherapy to treat eye cancer

Summary: Conjunctival melanoma is a highly aggressive and infiltrative type of mucosal melanoma. It has a high (>33%) recurrence rate, associated with metastasis in approximately 25% of patients. Gold standard treatment involves total surgical excision combined with adjuvant therapy, including topical chemotherapy.

The supervisors have previously optimised a mucoadhesive patch to deliver drugs to a different mucosal environment, the oral cavity. Here, the student will fabricate a new mucoadhesive patch, comprising a composite of peptide hydrogels and electrospun fibres, to achieve local delivery of the anti-cancer agent, mitomycin-C to the ocular surface.

Objectives:

1. Design, fabricate and characterise gel-fibre composites with a range of material properties, including degree of mucoadhesivity. 2. Incorporate mitomycin-C into the composite and optimise its release. 3. Determine composite function and efficacy in a 3D cancer invasion model. Experimental Approach:

The study involves three phases; tasks 1 and 2 are in iterative cycles

1) Hydrogel-fibre composite production. Our existing material libraries (poly(e-lysine) , polyester and mucoadhesive-friendly families) and fabrication technologies (bioink printing, melt electrowriting, electrospinning) will be used to create hydrogel-fibre composites of variable design and composition. Material characterisation will include surgical handling and mucoadhesive interaction with ex vivo tissues.

2) Creating drug-releasing gel-fibre composites. Mitomycin-C will be loaded into the composite and optimal drug concentration and release in vitro determined. Biological analyses will include cytotoxicity to normal and melanoma conjunctival cell lines and ability to minimise off-target effects.

3) Establishment of 3D conjunctival invasion model. The chick embryo model will be used to assess the ability of candidate composites to reduce conjunctival melanoma cell invasion.