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.

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Thus, the nanocurcumin hydrogel improved the wound healing process in diabetic skin of type 1 diabetic rats as compared with normal curcumin hydrogel [201]. In another study, self-assembled curcumin nanoparticles were encapsulated within gelatine microspheres to respond to matrix metalloproteinase 9 (MMP-9) which is commonly over-expressed at diabetic wound sides [202]. Thermosensitive hydrogel in the structure of curcumin-assembled gelatine microspheres was found to improve the capacity of drug release in a sustained manner to the diabetic wound and promoted the efficacy of healing via reducing redox stress and reversing MMP-9-provoked inhibition of cell migration in diabetic mice [202].…”

“…In another study, self-assembled curcumin nanoparticles were encapsulated within gelatine microspheres to respond to matrix metalloproteinase 9 (MMP-9) which is commonly over-expressed at diabetic wound sides [202]. Thermosensitive hydrogel in the structure of curcumin-assembled gelatine microspheres was found to improve the capacity of drug release in a sustained manner to the diabetic wound and promoted the efficacy of healing via reducing redox stress and reversing MMP-9-provoked inhibition of cell migration in diabetic mice [202]. Katas and co-researchers formulated a pluronic F-127-based gel containing curcumin-PGT (prostaglandin transporter) DsiRNA chitosan nanoparticles to treat diabetic wounds [203].…”

Advances and Impact of Antioxidant Hydrogel in Chronic Wound Healing

“…It has also been suggested that wound dressings should enhance leukocyte migration, prevent infection, remove excessive exudates, promote gas exchange, and even provide heat insulation and prevent reinjury . Therefore, functional hydrogels were developed, which were mainly made of materials with good biocompatibility and biodegradability, and were endowed with various functions (such as antioxidative, antimicrobial, anti‐inflammatory, and injectable) . Research shows that multifunctional hydrogels with good biocompatibility are the best choice for biomedical and pharmaceutical applications because they can achieve multistage and multifunctional combination therapy .…”

“…Many hydrogels have been reported by successfully loading and delivering curcumin to achieve antioxidant, and the therapeutic effect is remarkable. In a recent study, Wang and co‐workers developed a novel antioxidant hydrogel by loading with curcumin. The results showed that the antioxidant hydrogel could induce drug release in wound bed, and had the ability of antioxidation, which could effectively promote chronic wound healing.…”

“…As described above, multifunctional hydrogels can not only effectively prevent foreign matters and bacteria in the air from invading the wound, but also promote healing from deep mechanisms (such as antioxidation), which greatly improved the healing rate of chronic wounds . Recently, a large number of antioxidant hydrogels have appeared in the field of chronic trauma treatment, and a series of progress and success have been achieved . It can be seen that the development of hydrogel dressings is moving toward stabilization and high efficiency.…”