Plasma-activated antimicrobial hydrogel therapy (PAHT) for combating infections in diabetic foot ulcers

Lead Research Organisation: University of Bath
Department Name: Chemistry

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

10 25 50
 
Description The current project is 2 years into a 3 year EPSRC funded programme (EP/V00462X/1). Progress has been more rapid than envisaged, with the composite hydrogel concept not actually foreseen in the EPSRC application until year 3. The composite hydrogel wound dressing component allows for encapsulation of virtually any cationic antimicrobial and has been demonstrated using gentamicin, Ag ions, cetrimide, polymyxin B and PHMB.

The composite invented / discovered in this grant has the following attributes:

• Antimicrobials are released 'on-demand' following intervention of a clinician: either as part of routine care i.e., a daily or two daily bolus; or as a result of clinical suspicion i.e. elevated systemic temperature of the patient or peri-wound redness.
• Spatial control of antimicrobial release: only parts of the dressing need to be activated.
• Controlled release of the antimicrobial from the dressing can be achieved by controlling the CAP exposure time.
• Robust evidence of antimicrobial release at concentrations well above the minimum inhibitory concentration (MIC) / minimum bactericidal concentration (MBC) being effected over >14 days following daily CAP application (see figure X).
• Dressing can be left on the wound for > 14 days, potentially used in tandem with an absorbent secondary dressing for exudate management. This avoids disturbing the re-epithelializing wound bed; reduces likelihood of infection; reduces nursing care and reduces pain.
• CAP raises oxygen tension in wound, helping healing and inhibition of anaerobic bacteria.
• CAP generated species such as H2O2, which is disinfecting in nature, can be delivered to the wound thus enhancing the disinfecting effect.
• Compatible with PHMB which is widely touted as the general replacement for Ag in coming years (for reasons discussed in 4.3). PHMB has an excellent activity and safety profile [1,2].
• Versatile: will work with a wide range of other antimicrobial moieties, from antibiotics to antimicrobial peptides to small molecules and polymers.
• Comprised of low-cost commodity polymers, both made at the billion-tonne scale. PAA is a primary component of disposable nappies and costs ca. £2000 / tonne.
• Easy to manufacture: Preparation of wound dressing simply involves mixing polymers, swelling in antimicrobial solution of choice, heating then casting in a mould and freeze-thawing to cross-link.
• Plasma medicine is an emerging field, but commercial CE-marked CAP jets are already used in some clinics.

1. https://health.ec.europa.eu/system/files/2018-03/sccs_o_204_0.pdf
2. https://doi.org/10.1093/jac/dkv474
Exploitation Route Pre-clinical development (2024-2027)
1st in human study: 2028
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Title Composition 
Description Field of Invention The present invention relates to composite hydrogels comprising 5 at least one active pharmaceutical ingredient that can be selectively released from the hydrogel for delivery to a patient. Summary of the Invention According to a first aspect of the invention, there is provided a composite hydrogel comprising an anionic or cationic functional group-containing polymer and at least one active pharmaceutical agent (API), wherein the API is oppositely charged to the anionic or cationic functional group-containing polymer. One challenge in designing hydrogels for delivery of APIs to skin, wounds or other topical areas is to trigger drug release following a specific stimulus. It is undesirable to have slow passive release from a hydrogel dressing if the drug being eluted is present in concentrations below its therapeutic limit. The composite hydrogel described herein allows at least one API to be delivered to skin, wounds or other topical areas under specific conditions in a dose-controllable and reproducible manner. A second aspect of the invention provides a method of displacing an active pharmaceutical ingredient from a composite hydrogel according to the first aspect of the invention, the method comprising a step of treating the composite hydrogel with an ion source. A third aspect of the invention provides a wound dressing comprising the composite hydrogel of the first aspect of the invention. A fourth aspect of the invention provides a method of treating a wound comprising the steps of: (a) applying the wound dressing of the third aspect of the invention or the composite hydrogel of the first aspect of the invention to a wound, and (b) displacing the at least one active pharmaceutical ingredient by the method described in the second aspect of the invention. A fifth aspect of the invention provides a method of delivering an API to a patient comprising the steps of: (a) applying the composite hydrogel of the first aspect of the invention to a patient, and (b) displacing the at least one active pharmaceutical ingredient by the method described in the second aspect of the invention. 
IP Reference  
Protection Patent / Patent application
Year Protection Granted 2022
Licensed No
Impact Plan to licence to Plasma-4 Ltd in next 6 months
 
Company Name PLASMA4 LIMITED 
Description Plasma4 is a micro SME founded to develop the technology discovered in the grant towards clinical use. Professor Rob Short (CI) at Lancaster is the founder and director. 
Year Established 2021 
Impact None - yet, it is only 4 months old.
 
Description Online talk at POLY-CHAR 2022 international conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Conference talk at POLY-CHAR 2022 on the composite hydrogel system developed at Bath
Year(s) Of Engagement Activity 2022
URL https://poly-char2022.org/
 
Description Talk at Eton College Science Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Around 60 students and teachers from Eton college came to my talk on wound disinfection, plasma and hydrogels
Year(s) Of Engagement Activity 2022