Cold Atmospheric Plasma Activated Hydrogels for On Demand Drug Delivery

Abstract

This thesis focuses on the development and optimisation of smart hydrogel systems for the on-demand delivery of antimicrobials following the application of cold plasma.

Chapter 1 introduces key concepts such as wounds, wound healing, bacteria and infection, antimicrobials and antimicrobial resistance, along with hydrogels and plasma medicine. A review of current literature is provided to showcase recent studies relating to smart hydrogels and plasma activated hydrogels. The aims and objectives for this thesis are then presented to provide insight into topics that will be investigated herein.

Chapter 2 provides information and theory on key instrumentation and apparatus, along with details on the materials used. Experimental details are consolidated in this chapter to provide a comprehensive guide to all methods used in this thesis.

Chapter 3 presents the development and adaptation of assays used in further chapters for the quantification of antimicrobial release from cold plasma-activated hydrogel samples. This includes the use of dyes as model antimicrobials, chemical assays for drug release such as the ninhydrin assay, and bacterial inhibition assays such as MIC-style dilution assays, KB testing, and 96-well plate biofilm models.

Chapter 4 investigates the optimisation and use of a polyvinyl alcohol and sodium polyacrylate composite hydrogel for the controlled delivery of antimicrobials (polymyxin B, gentamicin and AMC-109). This chapter includes mechanistic studies, such as treatments to investigate responsiveness of the hydrogels to ionic strength, pH, and thus cold plasma. Release of polymyxin B is studied in detail, including a 7-day study where drug release is quantified each day using the ninhydrin assay, aiming to evidence the clinical potential of such a dressing. Microbiology assays are also conducted, proving efficacy of the drug released from the
hydrogel system using both planktonic and biofilm forms of P. aeruginosa. Additionally, polyacrylamide is tested as an alternative to polyvinyl alcohol, using both rheology measurements and drug release experiments for comparison.

Chapter 5 explores the use of a chemically crosslinked polyacrylate hydrogel, aiming to see if improvements on drug delivery could be made compared to the composite hydrogel system. A poly(acrylamide-co-acrylate) hydrogel is also tested for the same purpose. Preparation is conducted using standard reagents, including ammonium persulphate and N,N,N’,N’-Tetramethylethylenediamine as initiators, but notably the reaction is performed in a 12-well microtiter plate at RTP and under ambient air. Swelling capacities and storage/loss moduli of all hydrogel systems are measured to characterise the samples, followed by mechanistic dye release studies exploring pH and ionic strength responsiveness of the hydrogel samples. Cold plasma treatment is also examined for potential release of methylene blue and various antimicrobials, including polymyxin B.

Chapter 6 aims to develop a shear thinning, injectable hydrogel system that can be used in tandem with cold plasma for the release of antimicrobials. This work aspires to produce a conformable wound dressing that can be used for surgical wounds, implants, and deep burn wounds, where typical dressings would not be appropriate for use and instead require a mouldable material. Preliminary work begins to formulate an injectable gel that would be suitable for drug loading and cold plasma treatment, where use of biopolymers such as cellulose derivatives and sodium alginate are employed. These systems are tested using a rheometer to confirm shear-thinning and thixotropic behaviour, followed by experimenting with dye release using salts, acids, and cold plasma. Initial studies into antimicrobial release are trialled using bacterial inhibition assays and disc diffusion assays, although continued research is required to advance the system further.

Chapter 7 includes concluding remarks and suggestions for subsequent investigation that would provide a deeper understanding to the hydrogel systems discussed in this thesis, along with additional developments that could be made.

Date of Award	22 Jul 2026
Original language	English
Awarding Institution	University of Bath
Supervisor	Toby Jenkins (Supervisor) & Maciek Kopec (Supervisor)