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. 2017 Nov;48(11):2417-2425.
doi: 10.1016/j.injury.2017.08.046. Epub 2017 Aug 25.

Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats

Jean Carlos Fernando Besson  1 , Luzmarina Hernandes  1 , Jéssica Men de Campos  1 , Karina Amélia Morikawa  1 , Ciomar Aparecida Bersani-Amado  2 , Graciette Matioli  3
Affiliations

Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats

Jean Carlos Fernando Besson et al. Injury. 2017 Nov.

Abstract

Introduction: Skin lesions are a significant public health problem, above all that wounds fail to heal properly and become chronic. Due to its reepithelization action, insulin has the potential to heal skin lesions, by stimulating the proliferation and migration of keratinocytes, angiogenic stimulus, and increasing collagen deposition. In the present study insulin was complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and its wound healing effect and inclusion complex (HPβCD-I) were evaluated in excisional wounds in the skin of rats.

Material and methods: Three different gel based pharmaceutical forms were created: carbopol 940® base gel, an insulin gel comprising the base gel plus 50 IU of insulin and a gel complex comprising the base gel plus (HPβCD) complexed with insulin (HPβCD-I) were used to verify wound healing in vitro and in vivo assays.

Results: The wounds in the skin of rats were treated with gel containing HPβCD-I not cytoxically irritating and cytotoxic. Analysis of cell proliferation and measurement of the length and thickness of the epidermis showed that HPβCD-I prolonged the proliferation and migration of keratinocytes. Revascularization analysis of lesions treated with HPβCD-I compared to those treated with insulin found that angiogenic stimulus was less intense, but more constant and prolonged in the modified release process. There was increased deposition of type I and III collagen fibers in accordance with the treatment time.

Conclusion: Therefore, the slow release of complexed insulin modulated the reepithelialization process by stimulating cell proliferation and migration of keratinocytes, favoring greater concentration of serum insulin, modulating inflammatory response, matrix remodeling and promoting neovascularization. Angiogenesis extended by the steady release of insulin can be effective in the treatment of chronic wounds.

Keywords: Angiogenesis; Chronic wounds; Collagen; HPβCD-I; Inclusion complex; Inflammation; Insulin; Migration; Proliferation; Wound healing.

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