Hybrid Hydrogel Loaded with Chlorhexidine⊂β-CD-MSN Composites as Wound Dressing

Abstract

Background Much attention has been paid to sustained drug release and anti-infection in wound management. Hydrogels, which are biocompatible materials, are promising tools for controlled drug release and infective protection during wound healing. However, hydrogels also demonstrate limitations in the highly efficient treatment of wounds because of the diffusion rate. In this work, we explored pH-sensitive hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. Methods We constructed a hybrid gelatin methacrylate (GelMA) system with sustainable antibacterial properties combining hyaluronic acid (HA)-coated mesoporous silica nanoparticles (MSN), which loaded host-guest complexes of chlorhexidine (CHX) with β-cyclodextrins (β-CD) (CHX⊂CD-MSN@HA@GelMA). The release mechanism of CHX was explored using UV-vis spectra after intermittent diffusion of CHX. The hybrid hydrogels were characterized, and the drug content in terms of the release profile, bacterial inhibition, and in vivo experiments were investigated. Results Except for dual protection from both hydrogels, MSN in the HA improved the drug loading efficiency to promote the local drug concentration. It showed that complicated CHX-loaded MSN releases CHX more gradually and over a longer duration than CHX-loaded MSNs. This demonstrated a 12-day CHX release time and antibacterial activity, primarily attributable to the capacity of β-CD to form an inclusion complex with CHX. Meanwhile, in vivo experiments revealed that the hydrogels safely promote skin wound healing and enhance therapeutic efficacy. Conclusion We constructed pH-sensitive CHX⊂CD-MSN@HA@GelMA hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. The combination of β-CD and MSN would be better suited to release a reduced rate of active molecules over time (slow delivery), making them great candidates for wound dressing anti-infection materials.

Unveiling the versatility of gelatin methacryloyl hydrogels: a comprehensive journey into biomedical applications

“…This prolonged release, lasting for 12 d, displayed substantial antibacterial action, principally attributed to the capability of β-CD to build an inclusion complex with CHX. In vivo tests further suggested that the hydrogels efficiently facilitated wound healing of skin and improved therapeutic effectiveness [228]. Do Nascimento et al in another study, aimed to develop and evaluate the healing characteristics of GelMA enriched with aqueous extract of Punica granatum, gallic acid (GA), or ellagic acid (EA) in a rodent model.…”

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid

“…To control and prolong the release of drugs, HA was used as an NP coating, thus enhancing a stable and long-lasting repair effect on wound healing. Lin et al [82] described a new type of pH-sensitive wound dressing obtained by combining a hybrid gelatin methacrylate system with chlorhexidine-loaded silica NPs coated with HA. In vitro analysis demonstrated that this hydrogel provided an ultra-long-acting drug release with no cytotoxic effect on L929 fibroblast cells and a sustained antibacterial activity against S. aureus and E. coli.…”

Strategies to Regulate the Degradation and Clearance of Mesoporous Silica Nanoparticles: A Review

“…Their unique properties have positioned them as a significant focus of research and development as nanocarriers in drug delivery. [1][2][3][4][5][6][7][8][9][10][11][12] However, many studies have reported that slow biodegradability of MSNs could lead to severe particle bioaccumulation, potentially resulting in biosafety problems. [13][14][15][16] Generally, the degradation process of MSNs took several days, and the excretion of MSNs took several weeks from the body.…”