MICA: Antimicrobial bandage contact lenses

Lead Research Organisation: University of Liverpool
Department Name: Institute of Ageing and Chronic Disease

Abstract

The cornea is the clear window at the front of the eye. Following surgery or various treatments to the cornea a bandage contact lens will frequently be used to protect the cornea and increase comfort for the patient. To reduce the risk of infection antibiotics will also normally be administered.
In this project we will create a new type of contact lens that will combine both these processes. We have developed a novel hydrogel with a high water content, excellent transparency and mechanical properties similar to those of existing hydrogel contact lenses. The specific advantage of this new hydrogel is that it is naturally antimicrobial, unlike any of the existing materials. The hydrogel is synthesised in water at room temperature, whereas existing contact lens materials require the use the toxic solvents during synthesis and then need extensive washing procedures to remove them. We have shown that the novel hydrogel can be cast into a contact lens using existing moulding processes. We hypothesise that use of an antimicrobial bandage contact lens post-surgery or after an intervention such as corneal crosslinking, would increase comfort and reduce infection. In this study we will optimise the composition of the new hydrogel, fully characterise its antimicrobial and biocompatibility properties and evaluate its safety in a human healthy volunteer trial.
A second strand of this study will develop a therapeutic contact lens. Corneal infection is one of the commonest conditions affecting the cornea, accounting for 5% of cases of blindness worldwide. Contact lenses worn for vision are associated with a six fold increase in corneal infection. Treatment of corneal infection relies on frequent application of antibiotic drops; routinely every 5-15 minutes for the first 48 hours, then 2-6 hourly over 1-2 weeks. Contact lenses delivering therapeutic doses of antimicrobial drugs in a sustained and controlled manner would provide a more effective treatment strategy and augment conventional treatments. Corneal infection can be caused by both bacteria and fungi with each particular species requiring a different anti-infection drug treatment. We have demonstrated that our novel hydrogel can be loaded with antibiotic and antifungal drugs that are released at therapeutic levels that can kill bacteria and fungi in culture. In this study we will optimise the composition of the hydrogel to develop bandage contact lenses containing specific antibiotic and antifungal drugs that are used to treat corneal infections. We will fully characterise their anti-infection and cell compatibility properties in laboratory experiments using bacteria, fungi and corneal cells in culture and in an organ culture model of the front of the eye. Furthermore we will investigate if the bacteria and fungi species are able to develop resistance to the hydrogel with and without the added drugs using methods that analyse the genetic basis of antimicrobial resistance.
During this project we will collaborate with two companies; one with experience in the hydrogel synthesis and the other with extensive experience of contact lens manufacture. At the end of the project we intend to have 1) a bandage contact lens that is safe and has the potential to increase comfort for patients post corneal surgery and to reduce the risk of infection and 2) a therapeutic bandage contact lens that delivers clinically relevant antibiotics and antifungal drugs at therapeutic levels that have been shown to be effective at killing clinically relevant bacteria and fungi in the laboratory.

Technical Summary

Corneal infection is a significant clinical problem. Following corneal surgery a bandage contact lens (BCL) is frequently used to protect the cornea and increase comfort for the patient. To reduce the risk of infection antibiotics are also normally administered. Current BCLs comprise silicone-hydrogel, hydrogel or less commonly, collagen-based materials. None have antimicrobial activity. Our BCLs will be produced from high water content, transparent poly-e-lysine gels. We can cast these gels using existing contact lens moulds. We have shown that poly-e-lysine can be covalently attached to the gel surfaces and these were shown to be non-cytotoxic to human corneal epithelial cells in culture and did not inhibit healing in an in vitro corneal epithelial scratch assay model. We have demonstrated that these gels can significantly reduce the growth of Gram +ve (S. aureus) and Gram -ve (E. coli) cultures. We will develop these as prophylactic BCLs to reduce the risk of infection post-surgery and determine their safety in a human trial.
A second strand of this study will develop novel therapeutic BCLs. Treatment of corneal infection relies on frequent application of antibiotic drops; routinely every 5-15 minutes for the first 48 hours, then 2-6 hourly over 1-2 weeks. BCLs that deliver therapeutic doses of antimicrobial drugs in a sustained and controlled manner would provide a more effective treatment strategy and augment conventional treatments. We have demonstrated that Penicillin G (as a model antibiotic) and Amphotericin B (as a model antifungal) can be incorporated into the poly-e-lysine gels after synthesis through electrostatic attachment and have antimicrobial properties in vitro. We will optimise the properties of the poly-e-lysine gel lenses and their manufacture, incorporate clinically relevant antimicrobial agents to control major bacterial and fungal keratitis species using standard in vitro assays and an ex vivo corneal infection model.

Planned Impact

This is a translational project with the aim of developing a new class of bandage contact lenses that have excellent mechanical and handling properties, transparency, water content and have antimicrobial properties. Thus they will have impact in healthcare, commercial exploitation and in the academic community.
Healthcare: Many ophthalmologists advocate using a bandage contact lens after corneal surgery or intervention, such as corneal cross-linking, to enhance patient comfort. Currently they often also administer prophylactic antibiotics. This project will develop a bandage contact lens that is naturally antimicrobial with the aim of reducing the risk of infection in these patients without the need to administer antibiotics. This will be easier for the patients and clinicians as well as reducing the unnecessary use of antibiotics. Patients with corneal infection at present receive antibiotics via eye drops that need to be administered multiple times an hour early in the treatment. This project will develop bandage contact lenses that can deliver therapeutic levels of antibiotics over several hours. These lenses could provide clinicians with an additional and more effective treatment strategy and augment conventional treatments. This will have an impact on patients, their clinicians and their carers by improving patient compliance leading to fewer hospital admissions and thus reducing healthcare costs. Our clinical applicant will facilitate engagement with the clinical community to enhance uptake of the new treatment options.
Commercial: The aim of this project is to bring a new product onto the market via our collaboration with two industrial partners. We will also develop opportunities via these partners and with other companies to exploit the outputs from this project into other product areas. This could include tissue engineering applications and other drug delivery options. We will work closely through our TTO to develop new links and also use our existing contact with the HealthTech and Medicine KTN and the Precision Medicine and Cell and Gene Therapy Catapults.
Society: An advantage of the new hydrogel lenses to be developed in this project is that they are manufactured in more environmentally friendly processes than existing contact lens materials. This could have an impact on the environment. By working with our industrial collaborators we will ensure that the manufacturing process is optimised to take this into account. Part of the project will build an ex vivo corneal infection model which could reduce the need to perform as many in vivo animal experiments. This will help to fulfil the NC3Rs agenda as well as reducing costs in the development of future treatment strategies for corneal disorders.
Academic: Alongside the translational outputs this project has the potential to lead to high impact publications and an impact case study which will have impact for the academic team. Furthermore the strengthening of the cross-disciplinary collaboration by this project will underpin future academic grant applications. Throughout the project we will keep these aspects under discussion to ensure realisation of these impacts. The project will provide excellent training for the two PDRAs to develop their careers in this multidisciplinary area including both clinical and industrial input. The PDRAs will be provided with mentors to help them build personal development career plans.

Publications

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Kennedy SM (2020) Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa. in Investigative ophthalmology & visual science

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Kennedy Stephnie (2019) Antimicrobial activity of Poly-epsilon-lysine peptide hydrogels against Pseudomonas aeruginosa in INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

 
Description Antimicrobial Bandages for the Treatment of Wound Infections
Amount £854,545 (GBP)
Funding ID EP/P023223/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2020
 
Description Rapid, point of care diagnostic device for corneal infection
Amount £12,257 (GBP)
Organisation United Kingdom Research and Innovation 
Department Global Challenges Research Fund
Sector Public
Country United Kingdom
Start 11/2018 
End 03/2019
 
Description bandage contact lenses 
Organisation SpheriTech Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of novel hydrogel contact lenses
Collaborator Contribution Advise and materials
Impact three paper 6 conference presentations 3 postgraduate projects (PhD, MRes)
Start Year 2013
 
Description Improving the world though engineering - Engineering Day, Wirral Arts Festival (sponsored by IMechE) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture designed to highlight the breadth of engineering and how it influences our lives. It involved a lecture and a panel discussion to answer questions
Year(s) Of Engagement Activity 2019
 
Description Invited presentation at RAMS2019 (recent appointments in materials science) - Liverpool 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact RAMS2019 aims to connect and support early career academics and senior post-doctoral researchers in industry or academia working in Materials Science. The event involved being a plenary speaker as well as joining in the panel discussion to mentor and inspire early career academics and researchers.
Year(s) Of Engagement Activity 2019
 
Description Invited seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Research seminar to Biomedical Engineers at the University of Glasgow. Introducing the Ophthalmic Bioengieering research topic. Developing new collaborations
Year(s) Of Engagement Activity 2020
 
Description Materials to shape our vision; How advanced materials are fighting the loss of sight 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I presented to around 20 members of the general public in a pub. There was a lot of interest in the materials I showed them and this generated a lot of discussion. On the back of this i have been invited to take part in two more similar events
Year(s) Of Engagement Activity 2019
 
Description Public lecture to the Thirteen Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a presentation to an audience of around 70 retired professionals who organise a wide ranging programme of interesting presentations. I introuduced the importance of engineering and materials in overcoming vision loss. It generated a lot of interesting questions. I received very positive feedback, particularly around being able to present a complex subject in a very accessible way to the intellegent generalist.
Year(s) Of Engagement Activity 2020
 
Description SciBar presentation - Kirby, Liverpool 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation in a Pub in Liverpool to highlight sciences to the public
Year(s) Of Engagement Activity 2019
 
Description SciBar presentation Liverpool City Centre 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation in a Pub in Liverpool to highlight sciences to the public
Year(s) Of Engagement Activity 2019
 
Description Women in Engineering 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was an event organised by the IET to encourage young women into engineering careers by presenting the steps I had taken to build my career
Year(s) Of Engagement Activity 2019