Polyvinylpyrrolidone/hyaluronic acid-based bilayer constructs for sequential delivery of cutaneous antiseptic and antibiotic

After a skin injury, many complex metabolic events are triggered to ensure proper wound healing. Particularly for chronic, non-healing wounds or burns several risk factors such as persistent bacterial infections and fast dehydration can counteract the healing process. Intelligent wound dressings should help accelerate the healing process, while maintaining the wound bed clean and disinfected for several days at a time. Ideally, they should be self-adherent to both moist and dry skin surfaces and be transparent enough to allow prolonged wound inspection. These requirements pose challenges both in terms of materials science and pharmaceutics. Herein, we describe fabrication of a transparent bilayer construct for the sequential release and delivery of a cutaneous antiseptic and a widely used antibiotic, potentially suitable for wound dressing applications. The fabrication is a scalable waterborne and ecofriendly solution casting process. The first layer (for direct wound contact) is polyvinylpyrrolidone (PVP) containing a commercial antiseptic, Neomercurocromo® (Neo), while the second layer is a blend of hyaluronic acid (HA) and PVP containing ciprofloxacin. We show that the bilayer films have satisfactory self-adhering strength to human skin and that PVP and HA can interact via hydrogen bonds causing sustained release of the antibiotic over a period of 5 days. Biocompatibility was demonstrated on human foreskin fibroblast HFF-1 cells. Antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa while the wound resorption behavior was assessed through an in vivo full-thickness excisional wound healing mice model. These observations indicate that such bilayer constructs can be potentially implemented as wound care products for diverse range of skin wounds, including large area skin infections.