Ionically Crosslinked Chitosan Hydrogels for the Controlled Release of Antimicrobial Essential Oils and Metal Ions for Wound Management Applications

Abstract

The emerging problems posed by antibiotic resistance complicate the treatment regime required for wound infections and are driving the need to develop more effective methods of wound management. There is growing interest in the use of alternative, broad spectrum, pre-antibiotic antimicrobial agents such as essential oils (e.g., tea tree oil, TTO) and metal ions (e.g., silver, Ag+). Both TTO and Ag+ have broad spectrum antimicrobial activity and act on multiple target sites, hence reducing the likelihood of developing resistance. Combining such agents with responsive, controlled release delivery systems such as hydrogels may enhance microbiocidal activity and promote wound healing. The advantages of using chitosan to formulate the hydrogels include its biocompatible, mucoadhesive and controlled release properties. In this study, hydrogels loaded with TTO and Ag+ exhibited antimicrobial activity against P. aeruginosa, S. aureus and C. albicans. Combining TTO and Ag+ into the hydrogel further improved antimicrobial activity by lowering the effective concentrations required, respectively. This has obvious advantages for reducing the potential toxic effects on the healthy tissues surrounding the wound. These studies highlight the feasibility of delivering lower effective concentrations of antimicrobial agents such as TTO and Ag+ in ionically crosslinked chitosan hydrogels to treat common wound-infecting pathogens.

Antibacterial polysaccharide-based hydrogel dressing containing plant essential oil for burn wound healing

“…The reports have shown that the addition of essential oils to a matrix contributes toward reducing the required doses of the essential oils, while retaining their antioxidant-antimicrobial activity [ 32 ]. We hypothesized that the synergistic effects between essential oils and CBM/CMC enhanced the overall antimicrobial activity against E. coli and S. aureus , as the network structure of the CBM/CMC hydrogel delays the release of essential oils [ 33 ]. Plant essential oils, produced by plants as secondary metabolites, have been reported to possess effective bioactivity and biocompatibility owing to constituents such as terpenoids, phenolics and polyphenols [ 9 , 34 , 35 ].…”

Methylcellulose Hydrogel with Melissa officinalis Essential Oil as a Potential Treatment for Oral Candidiasis

“…In general, diffusion and drug release are affected by different parameters such as the hydrophilicity/hydrophobicity of the drug, the surface area and geometry of the hydrogel, the type and volume of solvent, the degradation of the hydrogel, the mesh size and the swelling rate [36]. Different volumes, solvents, ratios of hydrogel to solvent, flasks (e.g., universal, conical flasks), the presence of dialysis membranes and different shaking rate were found to be variable in a review of the literature [23,[37][38][39][40]. In the current study, the drug release was evaluated over 48 h, the amount of compounds released were a function of the initial content of oil.…”

In situ forming injectable hydrogels for drug delivery and wound repair

“…Even with the difficulties in maintaining homogeneity, ionically crosslinked hydrogels have demonstrated preliminary success when utilized as therapeutic depots, both for the treatment of antibiotic resistant biofilms 73 and the rapid regeneration or revascularization of damaged tissues 74 . Notably, Schmitt et al demonstrated that ionically crosslinked hybrid alginate/0.1% PEG/0.1% HA gels could be used as injectable carriers for the delivery of autologous mesenchymal stem cells (MSCs) into wound sites post injury 75 .…”