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Adv Wound Care (New Rochelle). 2017 Sep 1;6(9):279-288. doi: 10.1089/wound.2016.0725.

Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds.

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Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania.
Department of Orthopaedics and Rehabilitative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania.
Department of Ophthalmology, Penn State University College of Medicine, Hershey, Pennsylvania.


Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.


delayed cutaneous wound healing; diabetic rat; naltrexone

Conflict of interest statement

No ghostwriting was involved. Drs. Zagon, Sassani, and McLaughlin hold a U.S. patent related to naltrexone composition for wound healing, but they receive no financial income. There are no other disclosures related to any author.

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