Microneedle Patch for Transdermal Sequential Delivery of KGF‐2 and aFGF to Enhance Burn Wound Therapy

Abstract

AbstractSevere burn wounds usually destroy key cells’ functions of the skin resulting in delayed re‐epithelization and wound regeneration. Promoting key cells’ activities is crucial for burn wound repair. It is well known that keratinocyte growth factor‐2 (KGF‐2) participates in the proliferation and morphogenesis of epithelial cells while acidic fibroblast growth factor (aFGF) is a key mediator for fibroblast and endothelial cell growth and differentiation. However, thick eschar and the harsh environment of a burn wound often decrease the delivery efficiency of fibroblast growth factor (FGF) to the wound site. Therefore, herein a novel microneedle patch for sequential transdermal delivery of KGF‐2 and aFGF is fabricated to enhance burn wound therapy. aFGF is first loaded in the nanoparticle (NPaFGF) and then encapsulated NPaFGF with KGF‐2 in the microneedle patch (KGF‐2/NPaFGF@MN). The result shows that KGF‐2/NPaFGF@MN can successfully get across the eschar and sequentially release KGF‐2 and aFGF. Additional data demonstrated that KGF‐2/NPaFGF@MN achieved a quicker wound closure rate with reduced necrotic tissues, faster re‐epithelialization, enhanced collagen deposition, and increased neo‐vascularization. Further evidence suggests that improved wound healing is regulated by significantly elevated expressions of hypoxia‐inducible factor‐1 alpha (HIF‐1ɑ) and heat shock protein 90 (Hsp90) in burn wounds. All these data proved that KGF‐2/NPaFGF@MN is an effective treatment for wound healing of burns.