Encapsulation of Curcumin Nanoparticles with MMP9-Responsive and Thermos-Sensitive Hydrogel Improves Diabetic Wound Healing

Abstract

Impaired wound healing in diabetics usually leads to life-threatening complications. To develop a system for fastening skin wound healing efficiently and safely in diabetics, thermos-sensitive hydrogel containing the nanodrug, loaded in the form of gelatin microspheres (GMs), was designed to deliver curcumin (Cur) as a therapeutic drug. Cur is a naturally existing polyphenolic compound with a broad range of biological functions useful for potential therapies. Because Cur molecule has weakness in both bioavailability and in vivo stability, delivery of Cur requires assistance from other molecules to act as carrier vehicles in a sustained manner for therapeutic use. At first, self-assembly of Cur nanoparticles (CNPs) was done to improve bioavailability. The CNPs were further enclosed into GMs for responding to the matrix metalloproteinases (MMPs) that usually overexpress at diabetic nonhealing wound sites. The GMs containing CNPs were loaded into the thermos-sensitive hydrogel and were finally proved for the capacity of specially induced drug release at the wound bed, which promoted the efficacy in healing the standardized skin wounds in streptozotocin-induced diabetic mice. Our results indicated that the successfully developed CNP delivery system had the capacity to significantly promote skin wound healing, which suggested that it could have the potential to become a wound dressing with the properties of antioxidants and promotions of cell migration.

Keywords: MMP9-responsive; curcumin; diabetics; drug delivery system; non-healing wound.