Enhancement of Diabetic Wound Repair Using Biodegradable Nanofibrous Metformin-Eluting Membranes: in Vitro and in Vivo

Abstract

This work developed biodegradable nanofibrous drug-eluting membranes that provided sustained release of metformin for repairing wounds associated with diabetes. To prepare the biodegradable membranes, poly-d-l-lactide-glycolide (PLGA) and metformin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and were spun into nanofibrous membranes by electrospinning. An elution method and an HPLC assay were utilized to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. The biodegradable nanofibrous membranes released high concentrations of metformin for more than three weeks. Moreover, nanofibrous metformin-eluting PLGA membranes were more hydrophilic and had a greater water-containing capacity than virgin PLGA fibers. The membranes also improved wound healing and re-epithelialization in diabetic rats relative to the control. The experimental results in this work suggest that nanofibrous metformin-eluting membranes were functionally active in the treatment of diabetic wounds and very effective as accelerators in the early stage of healing of such wounds.

Efficient cutaneous wound healing using bixin-loaded PCL nanofibers in diabetic mice

“…Diabetes has been shown to impair immune function and decrease wound healing, both of which are critical to survival and recovery from major wound injury . Furthermore, hyperglycemia is a risk factor for epithelial down growth following skin injury.…”

“…Diabetes has been shown to impair immune function and decrease wound healing, both of which are critical to survival and recovery from major wound injury. 10 Furthermore, hyperglycemia is a risk factor for epithelial down growth following skin injury. A previous study demonstrated that Bixin promotes hypoglycemic activity 21 and mouth wound healing, 19 as well as improves the antioxidant response in different tissues.…”

“…6 Current treatments for ulcers or related wounds include administration of wound dressings or formulations such as hydrocolloids, hydrogels, foams, and films, 5,7 which may be employed as medicated systems through the delivery of healing enhancers (EGF, collagen, hyaluronic acid) 8 and therapeutic substances (drugs, peptides, growth factors, stem cells, and/or other bioactive substances). 5,[8][9][10][11][12] Moreover, the disadvantages of hydrogel forms and similar wound dressings include the inability to keep a stable shape, greater drying among others. For these reasons is necessary to establishing new alternatives for improving and reduce the adverse effects of other types of devices for wound healing.…”

Diabetes medications: Impact on inflammation and wound healing

“…However, a bioengineering group recently demonstrated that biodegradable nanofibrous drug-eluting membranes designed to sustainably release metformin, accelerated epithelization in wounds of STZ-injected diabetic rats. Specifically, the metformin-eluting membrane induced an 85% vs. 67% wound closure by day 7 and 97% vs. 85% closure by day 14 compared to non-eluting membrane treated wounds (Lee, Hsieh et al 2014). In addition, there is a large on-going Phase II clinical trial studying whether oral metformin (1000 mg three times a day) can help wound healing on burned children with expected results in 2017.…”

Electrospun nanofibrous materials for wound healing applications

“…Further, PLGA forms nontoxic end products, increases wettability, and promotes cell proliferation. Lee et al [47] used PLGA polymer for incorporating metformin, an antihyperglycemic agent usually prescribed for treating type 2 diabetes. The prepared metformin-incorporated PLGA nanofiber was investigated to treat wounds in diabetic SD rat model.…”