Subcutaneous low molecular weight heparin administration promotes wound healing in rats

Kuś, Ewa; Bieńkiewicz, Andrzej

doi:10.1016/j.pathophys.2006.01.001

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…In several clinical studies, patients treated with heparin for burns and diabetic foot injury exhibited enhanced capillary circulation that led to reduced wound healing time . The wound healing properties of subcutaneously administered Hp was investigated on burn wounds of rats by Kus and Bienkiewicz, which results in a significant reduction in wound healing time . Giraux et al have reported the heparin-dependent enhancement in cell migration of human umbilical vein endothelial cells (HUVEC) .…”

Section: Discussionmentioning

confidence: 99%

“…38 The wound healing properties of subcutaneously administered Hp was investigated on burn wounds of rats by Kus and Bienkiewicz, which results in a significant reduction in wound healing time. 39 Giraux et al have reported the heparin-dependent enhancement in cell migration of human umbilical vein endothelial cells (HUVEC). 12 Topical administration of a chitosan−heparin complex demonstrated encouraging results in the wound healing process.…”

Section: Discussionmentioning

confidence: 99%

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Heparin-Encapsulated Metered-Dose Topical “Nano-Spray Gel” Liposomal Formulation Ensures Rapid On-Site Management of Frostbite Injury by Inflammatory Cytokines Scavenging

Vaghasiya¹,

Sharma²,

Kumar

et al. 2019

ACS Biomater. Sci. Eng.

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The critical time window between the incidence of frostbite injury and the initiation of treatment in remote snowbound areas is a determining factor for an effective therapeutic response. It is an emergency condition and challenging to treat due to the poor vascularity of affected body parts, and it requires immediate action. In addition to cold trauma-induced tissue damage, the inflammatory mediators majorly contribute to pathologic aggravations. We have designed and evaluated a topical “nano-spray gel (NSG)” formulation, which is based on a combination of liposomal heparin sodium (Hp) and ibuprofen (Ibu) for rapid relief of frostbite injury in extremely low temperatures. The scientific literature suggests that heparin is associated with rapid endothelial cell repair, normalizing blood circulation in capillaries, and has a potential role in wound healing. Hp-containing liposomes were prepared by the extruder method, which suitably formulated an ibuprofen-containing gel to obtain a nano-Spray formulation (HLp-Ibu-NSG) applicable for topical delivery. A single spray puff of the formulation delivers ∼154 mg of the gel, which corresponds to ∼205 U of heparin. In this study, heparin liposomes exhibited significant healing of wound in vitro (scratch assay, fibroblast cells) and in vivo (wound healing in Sprague Dawley rats) at a low dose. In the rat model of frostbite injury, the HLp-Ibu-NSG formulation demonstrated significant reduction in the wound area (up to ∼96%) and improvement of histopathology in 14 days as compared to the control groups. No edema and erythema were detected post-treatment of HLp-Ibu-NSG in the affected area. The underlying mechanism was delineated as a modulation of the inflammatory cytokine (IL-6, TNF-α, IL-10, IL-4) mediators at the wound site and blood circulation to foster frostbite healing. Future clinical studies on the nano-spray gel are required to evaluate its efficacy for the treatment of frostbite symptoms. The instant on-site application of this formulation might be helpful in saving extremities of soldiers, mountaineers, and pilgrims having frostbite.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Heparin-Encapsulated Metered-Dose Topical “Nano-Spray Gel” Liposomal Formulation Ensures Rapid On-Site Management of Frostbite Injury by Inflammatory Cytokines Scavenging

Vaghasiya¹,

Sharma²,

Kumar

et al. 2019

ACS Biomater. Sci. Eng.

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“…Also Kus et al 22 performed a similar study for the same period and dose of application. Another dose problem of heparin studies on wound healing are direct comparison between UH and LMWH doses is not possible due to the differences in units.…”

Section: Discussionmentioning

confidence: 95%

Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats

et al. 2012

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PURPOSE:To compare the effects of unfractionated heparin (UH) and a low molecular weight heparin (LMWH) on skin wound healing of rats. METHODS: Forty eight male Sprague-Dawley rats underwent 8mm full thickness dorsal skin wounds and were randomly assigned to three equal groups. In experimental group A, heparin sodium was injected at a concentration of 1000U/kg. In experimental group B, enoxaparin was injected at a concentration of 1mg/kg. Physiologic saline (0.5ml) was administered to the control group. Injections were made subcutaneously, once daily, for seven days. At 7 th and 10 th days tissue samples were taken from all rats. Histologic examination of these tissues was made under light microscope and scored. RESULTS: Histological examination showed a significant difference between the 7 th and 10 th day groups in wound healing. It was observed that wound healing of LMWH injected group is better. This difference is statistically significant at 10 th day. CONCLUSIONS: Daily administration of single doses of unfractionated heparin and a low molecular weight heparin improves wound healing positively. Low molecular weight heparin induces wound healing more than unfractionated heparin.

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Controlled release of 2, 3 desulfated heparin exerts its anti‐inflammatory activity by effectively inhibiting E‐selectin

Lakshmi

Natesan

Shanmuganathan

et al. 2010

J Biomedical Materials Res

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Control of inflammation using appropriate anti-inflammatory agent prevents wound from becoming chronic. Heparin is a heterogeneous mixture of polysaccharide molecules with a mean molecular weight between 12-30 kDa containing 200-300 disaccharide units of glycosaminoglycan chains. Chemical modifications leading to generation of a unique pentasaccharide sequence effectively reduces its anticoagualant activity, while retaining its anti-inflammmatory property. In this study, Standard heparin was partially desulfated to 2, 3 desulfated heparin (2, 3 DSH) and its anti-inflammatory property was determined by assessing its ability to prevent static adhesion of leukocytes to endothelium and clotting assay. The effectiveness of 2, 3 DSH to down regulate E-selectin and key proinflammatory cytokines (IL-1beta and IL-6) was assessed by western blot and immunocytochemistry. These results were compared with commercially available 2-Desulfated Heparin (2DSH) and standard heparin (SH). Finally, a controlled delivery system of 2, 3 DSH was designed using chitosan microspheres and collagen as scaffold. Optimal loading of 2, 3 DSH was achieved and the release kinetics were tuned to follow a controlled release pattern. The steady state concentration of 2, 3 DSH was found to be optimal to elicit anti-inflammatory property and could achieve inhibition of E-selectin expression while unaffecting the normal clotting cascade.

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Subcutaneous low molecular weight heparin administration promotes wound healing in rats

Cited by 5 publications

References 18 publications

Heparin-Encapsulated Metered-Dose Topical “Nano-Spray Gel” Liposomal Formulation Ensures Rapid On-Site Management of Frostbite Injury by Inflammatory Cytokines Scavenging

Heparin-Encapsulated Metered-Dose Topical “Nano-Spray Gel” Liposomal Formulation Ensures Rapid On-Site Management of Frostbite Injury by Inflammatory Cytokines Scavenging

Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats

Controlled release of 2, 3 desulfated heparin exerts its anti‐inflammatory activity by effectively inhibiting E‐selectin

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