Biomaterial Database

Transdermal deferoxamine prevents pressure-induced diabetic ulcers. 2015

Dominik Duscher, and Evgenios Neofytou, and Victor W Wong, and Zeshaan N Maan, and Robert C Rennert, and Mohammed Inayathullah, and Michael Januszyk, and Melanie Rodrigues, and Andrey V Malkovskiy, and Arnetha J Whitmore, and Graham G Walmsley, and Michael G Galvez, and Alexander J Whittam, and Michael Brownlee, and Jayakumar Rajadas, and Geoffrey C Gurtner

Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305;

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

UI	MeSH Term	Description	Entries
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009336	Necrosis	The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D011312	Pressure	A type of stress exerted uniformly in all directions. Its measure is the force exerted per unit area. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Pressures
D003676	Deferoxamine	Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.	Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D003921	Diabetes Mellitus, Experimental	Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.	Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D000279	Administration, Cutaneous	The application of suitable drug dosage forms to the skin for either local or systemic effects.	Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013312	Stress, Physiological	The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.	Biotic Stress,Metabolic Stress,Physiological Stress,Abiotic Stress,Abiotic Stress Reaction,Abiotic Stress Response,Biological Stress,Metabolic Stress Response,Physiological Stress Reaction,Physiological Stress Reactivity,Physiological Stress Response,Abiotic Stress Reactions,Abiotic Stress Responses,Abiotic Stresses,Biological Stresses,Biotic Stresses,Metabolic Stress Responses,Metabolic Stresses,Physiological Stress Reactions,Physiological Stress Responses,Physiological Stresses,Reaction, Abiotic Stress,Reactions, Abiotic Stress,Response, Abiotic Stress,Response, Metabolic Stress,Stress Reaction, Physiological,Stress Response, Metabolic,Stress Response, Physiological,Stress, Abiotic,Stress, Biological,Stress, Biotic,Stress, Metabolic
D014456	Ulcer	A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.	Ulcers
D014945	Wound Healing	Restoration of integrity to traumatized tissue.	Healing, Wound,Healings, Wound,Wound Healings