Liposome-loaded biosynthetic bacterial cellulose hydrogels for wound management applications

Abstract

Chronic wounds and their management continue to present a huge financial burden to healthcare systems worldwide. With the population affected, expected to rise to 60 million people by 2026, there is a growing demand to produce novel wound dressing materials to facilitate effective wound healing. The invasion of pathogenic microorganisms at the site of the wound bed, can further stall the wound healing process. Infected, chronic wounds are responsible for significant morbidity and mortality rates across the globe, thus emphasis is placed on controlling infection and promoting an optimal wound environment, to enable rapid wound healing. Natural biosynthetic hydrogel wound dressings have revolutionised the field of wound management. Their unique properties and 3D fibrous network structure allow for the encapsulation of wound healing agents to enhance the wound healing process. In the present study, biosynthetic bacterial cellulose hydrogels were synthesised by Gluconacetobacter xylinus (ATCC 23770) and loaded with antimicrobial agents. Characterisation studies were carried out on these biosynthetic hydrogels for their wound healing properties. Due to the rise of antibiotic resistant bacterial strains, scientists are seeking other bioactive materials with wound healing properties. Silver has long been used as a broad-spectrum antimicrobial agent in creams and dressings for the purpose of wound healing over many years, however its tendency to cause skin irritation has limited its use. In comparison with traditional drug delivery systems, liposomes have the advantage of controlling drug release thus reducing toxic side effects, in addition to protecting drugs from degradation and clearance. In this study, liposomes were produced via the reverse-phase evaporation (REV) method. The antimicrobial activity of liposomal silver nitrate embedded in a biosynthetic bacterial cellulose hydrogel for wound management applications was investigated. Liposomal silver nitrate in a bacterial cellulose hydrogel exhibited antimicrobial activity against two representative wound infecting pathogens, specifically Pseudomonas aeruginosa and Staphylococcus aureus over a period of 48 hours. Silver exerted a stronger antimicrobial effect against P. aeruginosa compared with S. aureus due to differences in the structure of the bacterial cell walls. Nevertheless, liposomal silver nitrate in a bacterial cellulose hydrogel revealed broad-spectrum antimicrobial activity against both Gram-negative and drug resistant Gram-positive pathogenic bacterial strains. Furthermore, the drug release profile of liposomal silver nitrate embedded in bacterial cellulose displayed controlled silver release over 48 hours, indicating a potential decrease in toxic effects experienced compared with immediate release of silver nitrate when loaded directly into bacterial cellulose. The novelty aspect of my work lies in varying the surface charge of liposomes. A gap in the research suggested that antimicrobial efficacy of agents had not been tested when varying the surface charge of liposomes. Thus, liposomes with varied surface charge were formulated and investigated to optimise the antimicrobial delivery of agents to the wound site. Liposomal silver nitrate with an anionic surface charge embedded in a bacterial cellulose hydrogel exerted a stronger antimicrobial effect against the tested microbial strains compared with neutrally and cationic charged liposomal silver nitrate embedded in bacterial cellulose. This study confirmed that varying the charge density of the liposome structure can influence the liposomal characteristics, therefore enhance the formulation to provide optimal conditions for wound healing. The biosynthetic hydrogels exhibited antimicrobial activity against representative wound infecting pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. To conclude, the results indicate the potential of the investigated biosynthetic bacterial cellulose hydrogels for application in wound management. Further research aims to optimise the formulation by use of in vivo animal studies to represent a true wound microenvironment.