A multiphasic core-shell flurbiprofen and ciprofloxacin-loaded nanofibrous dressing cures infected burns via dual control of infection and inflammatory response

Abstract

Burn injury treatment is usually accompanied by significant challenges, like microbial growth and chronic inflammation. A multifunctional nanofibrous dressing with biphasic chemical properties is fabricated to regulate infection and inflammation in infected burns simultaneously. Hydrophobic polymer polycaprolactone (PCL) and hydrophilic polymer chitosan (CS) were used to manufacture a core-shell nanofibrous dressing that encapsulates the anti-inflammatory drug flurbiprofen (FLB) and the antibacterial drug ciprofloxacin (CIP). The dressings PCL-CS/FLB-CIP were characterized using TEM, FE-SEM, contact angle measurements, and FTIR spectroscopy. The phase boundaries in fibres result in a controlled release of both drugs, i.e., 70 h and 80 h, CIP and FLB, respectively, in vitro. It showed significant ROS scavenging activity and in vitro biocompatibility over NHDF cells, with good cell adhesion for up to 7 days. The in vitro antibacterial properties showed maximum inhibition at 50-60 hours against Staphylococcus aureus and Escherichia coli. Furthermore, the effect of FLB release demonstrated the immunomodulatory efficacy of the dressings when tested against macrophage-like THP-1 cells. Furthermore, the in vivo healing potential of the dressing was assessed in infected burns caused by Staphylococcus aureus in BALB/c mice, demonstrating significant healing by Day 18 compared to the untreated group. Bacterial growth inhibition, re-epithelization, neo-vascularization, collagen reappearance, and orientation were determined using the colony count method, H&E, MT, and VG staining, respectively. Also, evidence from IHC staining confirmed our secondary skin organ formation. The PCL-CS-based dual drug delivery system offers synergistic enhanced therapeutic efficacy and may provide a solution to the simultaneous challenges in burn wounds.