Optimization of transdermal deferoxamine leads to enhanced efficacy in healing skin wounds

Duscher, Dominik; Trotsyuk, Artem A.; Maan, Zeshaan N.; Kwon, Sun Hyung; Rodrigues, Mélanie; Engel, Karl; Stern‐Buchbinder, Zachary A.; Bonham, Clark A.; Barrera, Janos A.; Whittam, Alexander J.; Hu, Michael S.; Inayathullah, Mohammed; Rajadas, Jayakumar; Gurtner, Geoffrey C.

doi:10.1016/j.jconrel.2019.07.009

Cited by 44 publications

(38 citation statements)

References 39 publications

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“…Other studies report the effectiveness of DFOB as HIF-1α inducer and stabilizer through iron depletion, thereby promoting neovascularization and enhancing angiogenesis and wound maturation in mice. The simultaneous effects as iron chelator also include the prevention of oxidative stress and make DFOB a promising therapeutic agent to improve the healing of chronic wounds, with a pro-angiogenesis function [ 84 ].…”

Section: Dfob In Medicinal Chemistry and Other Applicationsmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, from the well-known iron chelation therapy to the most recent use in sensor devices. The three bidentate hydroxamic functional groups of deferoxamine B are the centerpiece of its metal binding ability, which allows the formation of stable complexes with many transition, lanthanoid and actinoid metal ions. In addition to the ferric ion, in fact, more than 20 different metal complexes of deferoxamine b have been characterized in terms of their chemical speciation in solution. In addition, the availability of a terminal amino group, most often not involved in complexation, opens the way to deferoxamine B modification and functionalization. This review aims to collect and summarize the available data concerning the complex-formation equilibria in solutions of deferoxamine B with different metal ions. A general overview of the progress of its applications over the past decade is also discussed, including the treatment of iron overload-associated diseases, its clinical use against cancer and neurodegenerative disorders and its role as a diagnostic tool.

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Section: Dfob In Medicinal Chemistry and Other Applicationsmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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“…), malnutrition, obesity, smoking, and microbial infection [ 5 , 6 , 7 , 8 , 9 , 10 ]. The cost of wound management is expensive, and the healthcare system spends more than $25 billion every year globally [ 11 , 12 ]. Wounds can also be categorized based on their depth as superficial wounds (damage of the epidermal lining), partial-thickness wounds (affecting both the epidermal and dermal layer), and full-thickness wounds (damage to both layers and other deep tissues and subcutaneous fat).…”

Section: Introductionmentioning

confidence: 99%

Electrospun Nanofibers/Nanofibrous Scaffolds Loaded with Silver Nanoparticles as Effective Antibacterial Wound Dressing Materials

et al. 2021

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The treatment of wounds is expensive and challenging. Most of the available wound dressings are not effective and suffer from limitations such as poor antimicrobial activity, toxicity, inability to provide suitable moisture to the wound and poor mechanical performance. The use of inappropriate wound dressings can result in a delayed wound healing process. Nanosize range scaffolds have triggered great attention because of their attractive properties, which include their capability to deliver bioactive agents, high surface area, improved mechanical properties, mimic the extracellular matrix (ECM), and high porosity. Nanofibrous materials can be further encapsulated/loaded with metal-based nanoparticles to enhance their therapeutic outcomes in wound healing applications. The widely studied metal-based nanoparticles, silver nanoparticles exhibit good properties such as outstanding antibacterial activity, display antioxidant, and anti-inflammatory properties, support cell growth, making it an essential bioactive agent in wound dressings. This review article reports the biological (in vivo and in vitro) and mechanical outcomes of nanofibrous scaffolds loaded with silver nanoparticles on wound healing.

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“…131 In a follow-up study, Duscher et al reported an enhanced transdermal DFO formulation that employed reverse micelle encapsulation but eliminated plasticizers, emulsifiers, and surfactants that were not compatible with FDA regulations. 132 The enhanced formulation also had increased surface area for drug release due to its microtextured surface and facilitated accelerated wound healing in a mouse model compared to DFO drip-on and DFO spray, as well as the original formulation. Interestingly, diabetic wounds treated with the enhanced transdermal formulation also demonstrated improved biomechanical properties compared to other methods of DFO administration.…”

Section: ■ Parkinson's Diseasementioning

confidence: 99%

“…Reverse micelle technology has also been employed to evaluate the effects of DFO treatment on outcome in an in vivo model of breast reconstruction after radiation . In a follow-up study, Duscher et al reported an enhanced transdermal DFO formulation that employed reverse micelle encapsulation but eliminated plasticizers, emulsifiers, and surfactants that were not compatible with FDA regulations . The enhanced formulation also had increased surface area for drug release due to its microtextured surface and facilitated accelerated wound healing in a mouse model compared to DFO drip-on and DFO spray, as well as the original formulation.…”

Section: In Nanoformulations Of Dfomentioning

confidence: 99%

Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer’s Disease, Parkinson’s Disease, and Intracerebral Hemorrhage

Farr

Xiong

2020

Mol. Pharmaceutics

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Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has also been implicated in the pathogenesis of Alzheimer’s disease (AD), Parkinson’s disease (PD), and secondary injury following intracerebral hemorrhage (ICH). Chelation of brain iron is thus a promising therapeutic strategy for improving behavioral outcomes and slowing neurodegeneration in the aforementioned disease states, though the effectiveness of DFO treatment is limited on several accounts. Systemically administered DFO results in nonspecific toxicity at high doses, and the drug’s short half-life leads to low patient compliance. Mixed reports of DFO’s ability to cross the blood–brain barrier (BBB) also appear in literature. These limitations necessitate novel DFO formulations prior to the drug’s widespread use in managing neurodegeneration. Herein, we discuss the various dosing regimens and formulations employed in intranasal (IN) or systemic DFO treatment, as well as the physiological and behavioral outcomes observed in animal models of AD, PD, and ICH. The clinical progress of chelation therapy with DFO in managing neurodegeneration is also evaluated. Finally, the elimination of intranasally administered particles via the glymphatic system and efflux transporters is discussed. Abundant preclinical evidence suggests that intranasal DFO treatment improves memory retention and behavioral outcome in rodent models of AD, PD, and ICH. Several other biochemical and physiological metrics, such as tau phosphorylation, the survival of tyrosine hydroxylase-positive neurons, and infarct volume, are also positively affected by intranasal DFO treatment. However, dosing regimens are inconsistent across studies, and little is known about brain DFO concentration following treatment. Systemic DFO treatment yields similar results, and some complex formulations have been developed to improve permeability across the BBB. However, despite the success in preclinical models, clinical translation is limited with most clinical evidence investigating DFO treatment in ICH patients, where high-dose treatment has proven dangerous and dosing regimens are not consistent across studies. DFO is a strong drug candidate for managing neurodegeneration in the aging population, but before it can be routinely implemented as a therapeutic agent, dosing regimens must be standardized, and brain DFO content following drug administration must be understood and controlled via novel formulations.

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Optimization of transdermal deferoxamine leads to enhanced efficacy in healing skin wounds

Cited by 44 publications

References 39 publications

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Electrospun Nanofibers/Nanofibrous Scaffolds Loaded with Silver Nanoparticles as Effective Antibacterial Wound Dressing Materials

Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer’s Disease, Parkinson’s Disease, and Intracerebral Hemorrhage

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