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Transdermal Drug Delivery Methods for Treatment of Chronic Skin Wounds
Affecting 5.7 million people in the US only, with an annual cost of $25 billion, chronic wounds are the leading cause of non-traumatic limb amputation. They create severe difficulties for individuals afflicted with this condition and a substantial financial burden for the healthcare industry. One of the most common symptoms of type 2 diabetes is slow tissue healing after injuries. Similarly, skin injuries in diabetic patients are slower to heal, and in many cases, can become chronic. Wound healing is an orchestrated cascade of physiological events. There are four healing phases that are commonly referred to as hemostasis, inflammation, proliferation, and maturation. However, in diabetic patients this cascade is interrupted, and diabetic ulcers and wounds can undergo continuous and excessive inflammation characterized by the presence of pro-inflammatory cells and cytokines. Delays longer than 90 days in the healing phase will make a wound become chronic. The dysfunctional physiology of chronic wounds makes them refractory to current wound therapy methods. Almost all the current wound care practices rely on the topical delivery of drugs. The dysfunctional pathophysiology of chronic wounds, which is an avascular, or not sufficiently vascularized tissue, covered by necrotic tissue and a crust accentuate the importance of the point of delivery on the effectiveness of therapeutics in wound healing. Our central hypothesis is that shortening the traveling distance of therapeutics by direct delivery of drugs into the live tissues below the necrotic layer could improve their effectiveness. Also, spatial and temporal controlled drug delivery in chronic wounds can increase the bioavailability and efficiency of wound therapy. To asses these hypotheses for chronic wound healing, miniaturized hollow needle arrays and liquid jet injectors were investigated for active, passive, and automated transdermal drug delivery. For passive drug delivery assessment, therapeutics were encapsulated in hydrogel and filled into the miniaturized needles. Then, the release profile and drug bioactivity were studied in vitro over time. Active drug delivery via miniaturized needles and liquid jet injectors resulted in accelerated wound healing in vitro and in vivo. The system was equipped with micropumps for precise drug dosing on a wireless platform with the capability of being controlled by a smartphone.
Aghabaglou, Fariba, "Transdermal Drug Delivery Methods for Treatment of Chronic Skin Wounds" (2020). ETD collection for University of Nebraska - Lincoln. AAI27670230.