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Title: A novel peptide hydrogel for an antimicrobial bandage contact lens
Author: Gallagher, A.
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Introduction: Corneal bandage lenses could have an important role to play in the treatment of corneal infection and disease. The application of bandage contact lenses for corneal ulcers are of interest as current treatment involves the topical administration of antibiotics, of which only 1 - 7% is absorbed to the site of infection. This inefficiency allows a lot of scope to improve the delivery of drugs to the surface of the eye. This study aimed to investigate the natural antimicrobial activity of a novel hydrogel as well as observing differences in activity when compounds such as additional poly-ε-lysine (pεK), penicillin G and amphotericin B were covalently or ionically coupled to the hydrogel. The ability to detect microbial keratitis pathogens was also investigated with the association of bacteria-identifying peptides to the hydrogel. Methods: Peptide hydrogels were synthesised from pεK cross-linked with octanedioic acid to densities of 0.067 - 0.1 g cm-3 and 45 - 80% cross-linking. The hydrogels were evaluated with a range of mechanical and physical tests. The hydrogels were also modified to bind additional pεK or the ionic association of penicillin G, amphotericin B or fluorescently labelled antimicrobial peptides. Hydrogel samples were incubated with E. coli, S. aureus or C. albicans and metabolic activity assays, plate counts and immunofluorescence techniques used to determine antimicrobial activity and the ability to identify microbes. Cytotoxicity of the hydrogels towards a human corneal epithelial cell line was monitored via a CCK-8 assay, scratch assay and antibody staining. Results: High water content (> 70%) hydrogels with comparable mechanical and physical properties to commercial contact lens materials were developed. A significant difference in antimicrobial activity was obtained by altering the surface properties of the hydrogel with either additional pεK or penicillin G compared to the LB agar control. Similar results for E. coli were observed. Hydrogels loaded with amphotericin B retained an antifungal activity against C. albicans under both normal conditions and in the presence of horse serum. The hydrogel demonstrated a drug release profile which was maintained above therapeutic levels for 72 h whilst amphotericin B stability was maintained for at least 48 h. The sorption of fluorescently labelled antimicrobial peptides to the hydrogel resulted in the successful labelling of both S. aureus and E. coli with no cytotoxicity towards HCE-T cells. Conclusion: Cross-linked pεK hydrogels with mechanical and physical properties comparable to commercial lens materials were developed. These alone were not antimicrobial towards E. coli, S. aureus or C. albicans, however, associating known antimicrobials with the free amine groups on the cross-linked hydrogel caused a significant antimicrobial effect. Furthermore, the association of fluorescently labelled antimicrobial peptides enabled the hydrogel to label bacteria. These modified hydrogels could have a role as bandage contact lenses in the diagnosis and treatment of corneal ulcers.
Supervisor: Williams, Rachel ; Elsheikh, Ahmed Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral