Engineering Personalised Cutaneous Hypobaric Microchambers to Facilitate the Treatment of Local Infectious Diseases with Gaseous Signalling Molecules

Lead Research Organisation: King's College London
Department Name: Pharmaceutical Sciences

Abstract

Plants release several volatile sulphur-containing compounds as a stress response. When scientists mimicked this plant response using sulphur-containing gases they inhibited fungal and bacterial growth on the surface of fruit. These results have important implications on food preservation, but in addition preliminary experiments by the King's College London and the University of Bath have shown that these gases can inhibit organisms that cause human skin and nail infections.

Despite the potential of gases to be used as anti-infective agents, it is difficult to use them with patients because gases do not readily pass into the body other than via the airways. However, reports have suggested that certain natural chemicals, e.g., allicin extract from garlic, can react once in the body to release a gas can be used to administer gases to the skin and nail. A medical device is now required that can control the deliver of these gases released by chemical donors such that they can effectively treat human infections.
Applying positive and negative pressure gradients to tissues can control the delivery of gases. For example, Continuous Positive Airway Pressure (CPAP) machines used with COVID-19 patients, increased the amount of oxygen in the blood by pushing the gas into the body under positive presure. If a device can be made that exerts negative pressure on the skin, then the gas delivered by a donor chemical will be released and held at the site of application to target its deliver and enhance its efficacy.

In this project, a customized 3D printed silicone sheath containing a microchamber that holds a gas donor chemical impregnated gauze on the nail surface, already designed by researchers at King's College London, will be refined and used to administer hydrogen sulphide to the nail for the treatment of nail infections. The microchamber and gauze will be customized to the exact region of the nail to be treated. This new device has the potential to treat over 100 million people who are thought to suffer from nail disease.

This research project will develop a new treatment paradigm for cutaneous infections. It will use personalised fabrication techniques, via commercially available benchtop 3D printers and digital 3D scanners, to provide patients with the flexibility to have effective treatments provided in the most user-friendly manner possible. The product will be a cost-effective solution to overcome a significant health problem as it facilitates the fabrication of a bespoke medical device from medical grade silicone materials using 3D printing (total cost of goods <50p). This approach could be developed to treat other skin infections including those arising as a consequence of chronic wounds and burns.

Publications

10 25 50
 
Description We have found that the ionised form of hydrogen sulphide passes through the human nail plate very effectively and is able to kill infections imbedded within the tissue.

We have found that enclosing a hydrogen sulphide donor within a medicated artificial nail that is attached to the nail provides highly effective permeation through the nail plate.
Exploitation Route Others may consider the use of therapeutic gases to treat microbial infections of hard and soft tissues.
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description HDHL
Amount £1,000,000 (GBP)
Funding ID BB/X002519/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2022 
End 06/2025
 
Description Collaboration with the University of Bath 
Organisation University of Bath
Department Department of Pharmacy and Pharmacology
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided data and information in order for the University of Bath to optimise the concentration of test agents to apply in the their mechanistic studies in to the effect of therapeutic gases in the kill of microorganisms and fungi.
Collaborator Contribution Our partners at Bath have designed fungal and microbial growth protocols and provided both organisms and man-power to run antimicrobial assays at King's.
Impact This is multidisciplinary involving pharmaceutical scientists from King's and microbiologists from Bath. All the outputs from the grant will arise from the collaboration.
Start Year 2021