Chitosan-Based Hydrogel for the Dual Delivery of Antimicrobial Agents Against Bacterial Methicillin-Resistant Staphylococcus aureus Biofilm-Infected Wounds

Abstract

Chronic wound infections caused by antibiotic-resistant bacteria have become a global health concern. This is attributed to the biofilm-forming ability of bacteria on wound surfaces, thus enabling their persistent growth. In most cases, it leads to morbidity and in severe cases mortality. Current conventional approaches used in the treatment of biofilm wounds are proving to be ineffective due to limitations such as the inability to penetrate the biofilm matrix; hence, biofilm-related wounds remain a challenge. Therefore, there is a need for more efficient alternate therapeutic interventions. Hydrogen peroxide (HP) is a known antibacterial/antibiofilm agent; however, prolonged delivery has been challenging due to its short half-life. In this study, we developed a hydrogel for the codelivery of HP and antimicrobial peptides (Ps) against bacteria, biofilms, and wound infection associated with biofilms. The hydrogel was prepared via the Michael addition technique, and the physiochemical properties were characterized. The safety, in vitro , and in vivo antibacterial/antibiofilm activity of the hydrogel was also investigated. Results showed that the hydrogel is biosafe. A greater antibacterial effect was observed with HP-loaded hydrogels (CS-HP; hydrogel loaded with HP and CS-HP-P; hydrogel loaded with HP and peptide) when compared to HP as seen in an approximately twofold and threefold decrease in minimum inhibitory concentration values against methicillin-resistant Staphylococcus aureus (MRSA) bacteria, respectively. Similarly, both the HP-releasing hydrogels showed enhanced antibiofilm activity in the in vivo study in mice models as seen in greater wound closure and enhanced wound healing in histomorphological analysis. Interestingly, the results revealed a synergistic antibacterial/antibiofilm effect between HP and P in both in vitro and in vivo studies. The successfully prepared HP-releasing hydrogels showed the potential to combat bacterial biofilm-related infections and enhance wound healing in mice models. These results suggest that the HP-releasing hydrogels may be a superior platform for eliminating bacterial biofilms without using antibiotics in the treatment of chronic MRSA wound infections, thus improving the quality of human health.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…Wound closure also improved in the groups treated with the coloaded hydrogel. [192] Scaffolds Film: Chitosan 50-190 kDa DDA: 75-85% S-nitrosoglutathione MRSA MRSA biofilm-infected wound model in mice: Both loaded and unloaded chitosan films reduced the bacterial burden in the wound and improved the healing rate compared to the control group.…”

Advances in Nanostructures for Antimicrobial Therapy

“…In addition, ablation of the biofilm matrix can be achieved using NPs producing magnetic, photothermal, or photodynamic effects as a response to external stimuli [ 110 , 111 , 112 ]. The ability of antibiotic-resistant bacteria on wound surfaces enables their continuous growth, resulting in chronic wound infections and subsequently leading to the morbidity or even to mortality [ 113 ]. The role of nanotechnology in combating biofilm-based antibiotic resistance was analyzed by Malaekeh-Nikouei et al [ 114 ] and micro- and nanosystems and biomaterials used for controlled delivery of antimicrobial and anti-biofilm agents contributing to fight-resistant microbes and biofilms were overviewed by Bianchera et al [ 115 ] Organic nanomaterials can effectively reduce the adhesion of biofilms, improve the permeability of antimicrobial agents, or attack the biofilm via specific actions and in such way that they can overcome the problems of bacterial biofilms, which predestine them to be used in the fight against biofilms [ 116 ].…”

“…Colloidal solutions of commercially available metal-based NPs including AgNPs (10 nm and 40 nm), AuNPs (20 nm), PtNPs (4 nm) and ZnO NPs, TiO 2 NPs, Al 2 O 3 NPs, Y 2 O 3 NPs and ZrO 2 NPs of 100 nm exhibited remarkable antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains and can be applied as coatings on 3D-printed biodegradable polymers, including bandages for chronic wounds, catheters, etc. [ 121 ] Biosafe hydrogels showing a porous structure enabling sustained release of the incorporated antibacterial drugs as well as convenient viscosity, are especially advantageous for topical applications [ 113 ]. By using a polymer-based antibiotic delivery system, including polymeric liposomes, polymeric micelles, highly branched polymers and dendrimers, and polymeric nanogels, improved therapeutic effects can be achieved in the treating of bacterial infections compared to free antibiotics [ 74 ].…”

Engineered Nanotechnology: An Effective Therapeutic Platform for the Chronic Cutaneous Wound

“…This demonstrates that the inclusion of AMPs is capable of creating a monumental variation in the effectiveness of the nanosystem. Furthermore, it also had a 10% higher wound closure capacity over HP-NPs [ 226 ].…”