Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control

Abstract

Burns and other skin injuries are growing concerns as well as challenges in an era of antimicrobial resistance. Novel treatment options to improve the prevention and eradication of infectious skin biofilm-producing pathogens, while enhancing wound healing, are urgently needed for the timely treatment of infection-prone injuries. Treatment of acute skin injuries requires tailoring of formulation to assure both proper skin retention and the appropriate release of incorporated antimicrobials. The challenge remains to formulate antimicrobials with low water solubility, which often requires carriers as the primary vehicle, followed by a secondary skin-friendly vehicle. We focused on widely used chlorhexidine formulated in the chitosan-infused nanocarriers, chitosomes, incorporated into chitosan hydrogel for improved treatment of skin injuries. To prove our hypothesis, lipid nanocarriers and chitosan-comprising nanocarriers (≈250 nm) with membrane-active antimicrobial chlorhexidine were optimized and incorporated into chitosan hydrogel. The biological and antibacterial effects of both vesicles and a vesicles-in-hydrogel system were evaluated. The chitosomes-in-chitosan hydrogel formulation demonstrated promising physical properties and were proven safe. Additionally, the chitosan-based systems, both chitosomes and chitosan hydrogel, showed an improved antimicrobial effect against S. aureus and S. epidermidis compared to the formulations without chitosan. The novel formulation could serve as a foundation for infection prevention and bacterial eradication in acute wounds.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…In addition to the intrinsic antimicrobial [22][23][24][25] and antifungal [26][27][28] activity of chitosan, this polymer exhibits anti-inflammatory activity [29][30][31], antioxidative effects [32,33], hemostatic activity [34,35], and healing properties [36][37][38]. Importantly, chitosan is both biocompatible [39,40] and biodegradable [41] and is approved by the U.S. Food and Drug Administration for certain applications [42]. These properties make chitosan an attractive building block in drug delivery systems and scaffolding.…”

Applications of Chitosan and its Derivatives in Skin and Soft Tissue Diseases

“…Chitosan and its derivatives exert antitumor activities and can, therefore, be potentially used in drug-delivery systems for the treatment of sarcoma ( Maleki Dana et al, 2021 ). Besides, chitosan-based nanoparticles, sponges, films, hydrogels, and scaffolds have been used for soft tissue injury treatment ( Oryan and Sahvieh, 2017 ; Hemmingsen et al, 2021 ; Rashki et al, 2021 ; Sun et al, 2021 ). Although chitosan and its derivatives have broad application prospects in the skin and soft tissue diseases, there is still a lack of review on this aspect.…”

Chitin and Chitosan: Prospective Biomedical Applications in Drug Delivery, Cancer Treatment, and Wound Healing

“…Chitosan has proven antimicrobial properties, which enable it to be used in combination with antimicrobial drugs in the treatment of acute skin injuries [ 72 , 73 ]. Topical skin diseases, however, require lipid-based vehicles such as liposomes because they have a better interaction with the skin and they can deliver drugs that are less soluble in the skin [ 73 ]. Liposomes, therefore, can be coated with chitosan to enhance antimicrobial activity during the treatment of skin and soft tissue infections (SSTIs) [ 73 ].…”

“…Topical skin diseases, however, require lipid-based vehicles such as liposomes because they have a better interaction with the skin and they can deliver drugs that are less soluble in the skin [ 73 ]. Liposomes, therefore, can be coated with chitosan to enhance antimicrobial activity during the treatment of skin and soft tissue infections (SSTIs) [ 73 ]. In a study by Hemmingsen and colleagues [ 73 ], liposomes containing antimicrobial drugs, Chlorhexidine (CHX), were incorporated into chitosan-based hydrogels to enhance liposome retention during drug release.…”

“…Liposomes, therefore, can be coated with chitosan to enhance antimicrobial activity during the treatment of skin and soft tissue infections (SSTIs) [ 73 ]. In a study by Hemmingsen and colleagues [ 73 ], liposomes containing antimicrobial drugs, Chlorhexidine (CHX), were incorporated into chitosan-based hydrogels to enhance liposome retention during drug release. It was found that chitosomes (chitosan-infused vesicles) incorporated with CHX cause a greater release of CHX and sustained therelease of CHX than the CHX formulations without chitosomes ( Figure 6 ) [ 73 ].…”