The Evaluation of the Effects of Nanoemulsion Formulations Containing Boron and/or Zinc on the Wound Healing in Diabetic Rats

Wound healing remains a challenging clinical problem, especially in the presence of diabetes. Diabetic patients have the impaired ability to fight infection and insufficient inflammatory response. The aim of this study was to evaluate the effects of boronophenylalanine (BFA) and/or Zn-containing nanoemulsion (NE) formulations on wound healing in diabetic rats. MTT and scratch assays were performed to evaluate the proliferative effects of BFA and/or Zn on human dermal fibroblast (HDF) cells and the migration of these cells, respectively. The BFA and/or Zn-NE were prepared, and the effects of NEs on wound healing in diabetic rats were evaluated by applying once a day for 14 days. MTT assay showed that 10 to 25 µM BFA and/or 50 µM Zn had very significant positive effects on cell proliferation. In the scratch assay, 10 µM BFA significantly increased the migration of HDF cell compared with control. The droplet sizes of all the NEs were <115 nm and their zeta potential values were in range of (−) 23.9 ± 2.356 to (−) 33.1 ± 1.438 mV. There was a significant reduction in the wound contraction values (%) of the groups treated with the BFA and/or Zn-NE on the 14th day compared with the untreated diabetic rats group. According to histopathological findings, wound healing was nearly complete in BFA and/or Zn-NE compared with untreated diabetic rats. Especially, the group treated with the NE containing the low concentration of BFA showed highly promising results in wound healing of diabetic rats within 14 days with complete epithelialization and the completely closed wound area.

[1]  A. Amani,et al.  Levofloxacin nanoemulsion gel has a powerful healing effect on infected wound in streptozotocin-induced diabetic rats , 2020, Drug Delivery and Translational Research.

[2]  N. Aksu,et al.  Evaluation of burn wound healing activity of novel fusidic acid loaded microemulsion based gel in male Wistar albino rats , 2020, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[3]  Xinyan Liu,et al.  Combination of essential oil from Zanthoxylum bungeanum Maxim. and a microemulsion system: Permeation enhancement effect on drugs with different lipophilicity and its mechanism , 2020 .

[4]  S. M. Davachi,et al.  Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model , 2020 .

[5]  R. Jani,et al.  A Review on Nanoemulsions: A Recent Drug Delivery Tool , 2019, Journal of Drug Delivery and Therapeutics.

[6]  O. Şenol,et al.  The Effect of Parietin Isolated From Rheum ribes L on In Vitro Wound Model Using Human Dermal Fibroblast Cells , 2019, The international journal of lower extremity wounds.

[7]  Kanokwan Kulprachakarn,et al.  Micronutrients and Natural Compounds Status and Their Effects on Wound Healing in the Diabetic Foot Ulcer , 2017, The international journal of lower extremity wounds.

[8]  G. Srisawasdi,et al.  An Asian Perspective on Povidone Iodine in Wound Healing , 2017, Dermatology.

[9]  E. Sağlam,et al.  Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial , 2017, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[10]  A. Sood,et al.  Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications. , 2017, Wounds : a compendium of clinical research and practice.

[11]  A. Doğan,et al.  Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation , 2016, Molecular and Cellular Biochemistry.

[12]  A. Boccaccini,et al.  Preparation and characterization of electrosprayed daidzein–loaded PHBV microspheres , 2015 .

[13]  L. Pizzorno Nothing Boring About Boron. , 2015, Integrative medicine.

[14]  A. Doğan,et al.  Boron and Poloxamer (F68 and F127) Containing Hydrogel Formulation for Burn Wound Healing , 2015, Biological Trace Element Research.

[15]  A. Desmoulière,et al.  Fibroblasts and myofibroblasts in wound healing , 2014, Clinical, cosmetic and investigational dermatology.

[16]  S. Honary,et al.  Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2) , 2013 .

[17]  E. Yurtov,et al.  Nanoemulsions: the properties, methods of preparation and promising applications , 2012 .

[18]  F. Nielsen,et al.  Growing Evidence for Human Health Benefits of Boron , 2011 .

[19]  Tomaz Velnar,et al.  The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms , 2009, The Journal of international medical research.

[20]  A. Akbarzadeh,et al.  Induction of diabetes by Streptozotocin in rats , 2007, Indian Journal of Clinical Biochemistry.

[21]  Marjana Tomic-Canic,et al.  Cellular and molecular basis of wound healing in diabetes. , 2007, The Journal of clinical investigation.

[22]  B. Dréno,et al.  In vitro induction of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 expression in keratinocytes by boron and manganese , 2004, Experimental dermatology.

[23]  T. Tadros,et al.  Formation and stability of nano-emulsions. , 2004, Advances in colloid and interface science.

[24]  O. Velev,et al.  Charging of Oil−Water Interfaces Due to Spontaneous Adsorption of Hydroxyl Ions , 1996, Langmuir.

[25]  W. Garvey Modified elastic tissue-Masson trichrome stain. , 1984, Stain technology.

[26]  S. Pollack The wound healing process. , 1984, Clinics in dermatology.

[27]  A. Koc,et al.  The importance of boron in biological systems. , 2018, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[28]  R. Dessordi,et al.  Boron action in bone health , 2017 .

[29]  E. J. Vernon‐Carter,et al.  PREPARATION AND CHARACTERIZATION OF CURCUMIN NANOEMULSIONS OBTAINED BY THIN-FILM HYDRATION EMULSIFICATION AND ULTRASONICATION METHODS , 2016 .

[30]  V. Torchilin,et al.  Nanopreparations for skin cancer therapy , 2016 .

[31]  E. Keleb,et al.  Nanoemulsion and nanoemulgel as a topical formulation , 2015 .

[32]  S. Saranya,et al.  Cinnamon oil nanoemulsion formulation by ultrasonic emulsification: investigation of its bactericidal activity. , 2013, Journal of nanoscience and nanotechnology.

[33]  A. Lansdown,et al.  Zinc in wound healing: Theoretical, experimental, and clinical aspects , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[34]  N. Halmi Differentiation of two types of basophils in the adenohypophysis of the rat and the mouse. , 1952, Stain technology.