Multifunctional Double-Layer and Dual Drug-Loaded Microneedle Patch Promotes Diabetic Wound Healing

Abstract

Chronic nonhealing diabetic wounds are a serious complication of diabetes, with a high morbidity rate that can cause disability or death. The long period of inflammation and dysfunctional angiogenesis are the main reasons for wound-healing difficulty in diabetes. In this study, a multifunctional double-layer microneedle (DMN) is constructed to control infection and promote angiogenesis, meeting the multiple demands of the healing process of a diabetic wound. The double-layer microneedle is consisted in a hyaluronic acid substrate and a mixture of carboxymethyl chitosan and gelatin as the tip. The antibacterial drug tetracycline hydrochloride (TH) is loaded into the substrate of the microneedle to achieve rapid sterilization and promote resistance to external bacterial infections. The microneedle tip loaded with recombinant human epidermal growth factor (rh-EGF) is inserted into the skin, in response to gelatinase produced by resident microbe and disassociate to achieve the enzymatic response release. The double-layer drug-loaded microneedles (DMN@TH/rh-EGF) have antibacterial and antioxidant effects, and promote cell migration and angiogenesis in vitro. In an in vivo diabetic wound model, using rats, the DMN@TH/rh-EGF patch is able to inhibit inflammation, promote angiogenesis, collagen deposition, and tissue regeneration during the wound healing process, promoting its healing.

Keywords: angiogenesis; antibacterials; microneedles; transdermal drug delivery; wound healing.