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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(®) 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.
PMID
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Topical Naltrexone as Treatment for Type 2 Diabetic Cutaneous Wounds.

Authors

Mayor MeshTerms
Keywords

delayed cutaneous wound healing

diabetic rat

naltrexone

Journal Title advances in wound care
Publication Year Start




PMID- 28894635
OWN - NLM
STAT- PubMed-not-MEDLINE
DA  - 20170912
LR  - 20170914
IS  - 2162-1918 (Print)
IS  - 2162-1918 (Linking)
VI  - 6
IP  - 9
DP  - 2017 Sep 01
TI  - Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of
      Diabetic Wounds.
PG  - 279-288
LID - 10.1089/wound.2016.0725 [doi]
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(R) 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.
FAU - McLaughlin, Patricia J
AU  - McLaughlin PJ
AD  - Department of Neural and Behavioral Sciences, Penn State University College of
      Medicine, Hershey, Pennsylvania.
FAU - Cain, Jarrett D
AU  - Cain JD
AD  - Department of Orthopaedics and Rehabilitative Medicine, Penn State University
      College of Medicine, Hershey, Pennsylvania.
FAU - Titunick, Michelle B
AU  - Titunick MB
AD  - Department of Neural and Behavioral Sciences, Penn State University College of
      Medicine, Hershey, Pennsylvania.
FAU - Sassani, Joseph W
AU  - Sassani JW
AD  - Department of Ophthalmology, Penn State University College of Medicine, Hershey, 
      Pennsylvania.
FAU - Zagon, Ian S
AU  - Zagon IS
AD  - Department of Neural and Behavioral Sciences, Penn State University College of
      Medicine, Hershey, Pennsylvania.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Adv Wound Care (New Rochelle)
JT  - Advances in wound care
JID - 101590593
PMC - PMC5592845
OTO - NOTNLM
OT  - delayed cutaneous wound healing
OT  - diabetic rat
OT  - naltrexone
COI - 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.
EDAT- 2017/09/13 06:00
MHDA- 2017/09/13 06:01
CRDT- 2017/09/13 06:00
PHST- 2017/01/02 [received]
PHST- 2017/03/13 [accepted]
AID - 10.1089/wound.2016.0725 [doi]
AID - 10.1089/wound.2016.0725 [pii]
PST - ppublish
SO  - Adv Wound Care (New Rochelle). 2017 Sep 1;6(9):279-288. doi:
      10.1089/wound.2016.0725.