• 2 Citations

Abstract

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.

LanguageEnglish (US)
Pages279-288
Number of pages10
JournalAdvances in Wound Care
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Naltrexone
Wounds and Injuries
Diabetic Foot
Platelet-Derived Growth Factor
Mast Cells
Vascular Endothelial Growth Factor A
Therapeutics
DNA
Foot Ulcer
Skin
Narcotic Antagonists
Fibroblast Growth Factors
Bromodeoxyuridine
Amputation
Health Care Costs
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Cytokines
platelet-derived growth factor BB

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

@article{d3e4197eacf54a009531777f1e686dda,
title = "Topical Naltrexone is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds",
abstract = "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{\circledR} 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.",
author = "McLaughlin, {Patricia J.} and Cain, {Jarrett D.} and Titunick, {Michelle B.} and Sassani, {Joseph W.} and Zagon, {Ian S.}",
year = "2017",
month = "9",
day = "1",
doi = "10.1089/wound.2016.0725",
language = "English (US)",
volume = "6",
pages = "279--288",
journal = "Advances in Wound Care",
issn = "2162-1918",
publisher = "Mary Ann Liebert Inc.",
number = "9",

}

TY - JOUR

T1 - Topical Naltrexone is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds

AU - McLaughlin,Patricia J.

AU - Cain,Jarrett D.

AU - Titunick,Michelle B.

AU - Sassani,Joseph W.

AU - Zagon,Ian S.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85028980370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028980370&partnerID=8YFLogxK

U2 - 10.1089/wound.2016.0725

DO - 10.1089/wound.2016.0725

M3 - Article

VL - 6

SP - 279

EP - 288

JO - Advances in Wound Care

T2 - Advances in Wound Care

JF - Advances in Wound Care

SN - 2162-1918

IS - 9

ER -