Optimization of transdermal deferoxamine leads to enhanced efficacy in healing skin wounds
| Autor: | Clark A. Bonham, Alexander J. Whittam, Dominik Duscher, Jayakumar Rajadas, Geoffrey C. Gurtner, Karl Engel, Zachary A. Stern-Buchbinder, Artem A. Trotsyuk, Mohammed Inayathullah, Janos A. Barrera, Michael S. Hu, Zeshaan N. Maan, Melanie Rodrigues, Sun Hyung Kwon |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Chronic wound Neovascularization Physiologic Siderophores Pharmaceutical Science 02 engineering and technology Deferoxamine Pharmacology Administration Cutaneous Neovascularization Mice 03 medical and health sciences Drug Delivery Systems Animals Humans Medicine Adverse effect Skin 030304 developmental biology Transdermal Wound Healing 0303 health sciences business.industry Regeneration (biology) 021001 nanoscience & nanotechnology Mice Inbred C57BL Drug Liberation Drug delivery Collagen medicine.symptom 0210 nano-technology business Wound healing medicine.drug |
| Zdroj: | Journal of Controlled Release. 308:232-239 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2019.07.009 |
| Popis: | Chronic wounds remain a significant burden to both the healthcare system and individual patients, indicating an urgent need for new interventions. Deferoxamine (DFO), an iron-chelating agent clinically used to treat iron toxicity, has been shown to reduce oxidative stress and increase hypoxia-inducible factor-1 alpha (HIF-1α) activation, thereby promoting neovascularization and enhancing regeneration in chronic wounds. However due to its short half-life and adverse side effects associated with systemic absorption, there is a pressing need for targeted DFO delivery. We recently published a preclinical proof of concept drug delivery system (TDDS) which showed that transdermally applied DFO is effective in improving chronic wound healing. Here we present an enhanced TDDS (eTDDS) comprised exclusively of FDA-compliant constituents to optimize drug release and expedite clinical translation. We evaluate the eTDDS to the original TDDS and compare this with other commonly used delivery methods including DFO drip-on and polymer spray applications. The eTDDS displayed excellent physicochemical characteristics and markedly improved DFO delivery into human skin when compared to other topical application techniques. We demonstrate an accelerated wound healing response with the eTDDS treatment resulting in significantly increased wound vascularity, dermal thickness, collagen deposition and tensile strength. Together, these findings highlight the immediate clinical potential of DFO eTDDS to treating diabetic wounds. Further, the topical drug delivery platform has important implications for targeted pharmacologic therapy of a wide range of cutaneous diseases. |
| Databáze: | OpenAIRE |
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