Treatment of PLGA Nanoparticles Ointment-Ethanol Extract of Archidendron pauciflorum in the Wound Healing in Diabetic Mice

Diabetic wounds lead to severe tissue damage and are diffi-cult to cure. Jengkol (Archidendron pauciflorum) is a plant commonly used by local Indonesian communities to treat diabetic wounds. The efficiency of herbal medicine still has a deficiency of its ability to reach the target organs, therefore nanotechnology is applied in the hope that all drug concentrations can reach the target organs successfully. This study aimed to evaluate the effectiveness of PLGA nanoparticle ointment-ethanol extract jengkol fruit peel (EEJFP) to accelerate the wound healing process in the skin of streptozotocin-induced diabetic mice. The research method used was experimental with a completely randomized design using six treatments and four replications. Diabe-tes was induced by intraperitoneal injection of streptozotocin 180 mg/ kg BW. Mice with a blood glucose level of ≥150 mg/dL were used for diabetic mice models. The incision wound created at the dorsolateral region of shaven skin at ±1 cm2 using sterile scissors. The treatments given were vaseline for Control Negative (CN) and Control Positive (CP), Betadine ointment (PB), 10% EEJFP ointment (P1), 5% PLGA nanoparticle ointment-EEJFP (P2), and 2.5% PLGA nanoparticle ointment-EEJFP (P3). The results showed that the administration of PLGA nanoparticles ointment-EEJFP with a concentration of 5% PLGA nanoparticle ointment-EEJFP (P2) resulted in the shortest wound length on day 3, 7 and 14; narrower granulation tissue; a larger number of blood capillaries; and denser collagen fibers (α <0.05) compared to CP and PB treatments. The administration of PLGA nanoparticle ointment-EEJFP with a concentration of 5% was the most effective concentration in accelerating wound healing in the skin of diabetic mice.

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Topical treatment of ointment containing ethanol extract of Archidendron pauciflorum fruit peel on the wound healing in streptozotocin-induced diabetic mice

Nusantara Bioscience ◽

10.13057/nusbiosci/n090311 ◽

2017 ◽

Vol 9 (3) ◽

pp. 306-311 ◽

Cited By ~ 1

Author(s):

DESAK MADE MALINI ◽

MADIHAH MADIHAH ◽

FITRI KAMILAWATI ◽

NINING RATNINGSIH ◽

KARTIAWATI ALIPIN ◽

...

Keyword(s):

Wound Healing ◽

Topical Application ◽

Topical Treatment ◽

Healing Process ◽

Ethanol Extract ◽

Negative Control ◽

Control Group ◽

Diabetic Mice ◽

Fruit Peel ◽

Diabetic Wounds

Malini DM, Madihah, Kamilawati F, Ratningsih N, Alipin K, Iskandar J. 2017. Topical treatment of ointment containing ethanol extract of Archidendron pauciflorum fruit peel on the wound healing in streptozotocin-induced diabetic mice. Nusantara Bioscience 9: 306-311. Diabetic wounds lead to severe tissue damage and are difficult to cure. One alternative medicine known well by local Indonesian communities to treat diabetic wounds is the fruit peel of djengkol. This study aimed to evaluate the ointment containing ethanol extract of djengkol fruit peel to accelerate wound healing process in the skin of streptozotocin-induced diabetic mice. The method was experimental using completely randomized design with six treatments and four replications. Diabetes was induced by intraperitoneal injection of streptozotocin 180 mg/kg BW. Mice with blood glucose level â‰¥150 mg/dL were used for diabetic mice models. The incision wound created at dorsolateral region of shaven skin at Â±1 cm2 using sterile scissors. The ointment containing extract was applied topically to the diabetic mice wounds at concentration of 5%, 10% and 15%, as well as BetadineÂ® as the reference group. The ointment basis was applied to the wound of diabetic mice as a positive control and to the wound of non-diabetic mice as a negative control. The treatment was done twice a day for 14 days. The results showed that topical application of ointment containing ethanol extract of djengkol fruit peel at concentration of 10% gave significant recovery (p<0.05) on the wounded skin by the enhancement of re-epithelization and granulation tissue, as well as the increase of capillary number and collagen density which were higher than other treatments and comparable to negative control group. It was concluded that the topical application of ointment containing ethanol extract of djengkol fruit peel can support the healing of diabetic wounds.

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Topical Gynura procumbens as a Novel Therapeutic Improves Wound Healing in Diabetic Mice

Plants ◽

10.3390/plants10061122 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1122

Author(s):

Nutda Sutthammikorn ◽

Volaluck Supajatura ◽

Hainan Yue ◽

Miho Takahashi ◽

Sunee Chansakaow ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Transforming Growth Factor ◽

Therapeutic Option ◽

Healing Process ◽

Unmet Need ◽

New Drugs ◽

Wound Healing Process ◽

Diabetic Mice ◽

Diabetic Wounds

Nonhealing wounds are major socioeconomic challenges to healthcare systems worldwide. Therefore, there is a substantially unmet need to develop new drugs for wound healing. Gynura procumbens, a herb found in Southeast Asia, may be an effective therapeutic for nonhealing diabetic wounds. The aim of this study was to evaluate the efficacy of G. procumbens on wound healing in the diabetic milieu. G. procumbens extract was obtained using 95% ethanol and its components were determined by thin layer chromatography. Diabetes was induced in mice using streptozotocin. We found that G. procumbens extract contained stigmasterol, kaempferol and quercetin compounds. Topical application of G. procumbens on the wounded skin of diabetic mice accelerated wound healing and induced the expression of angiogenin, epidermal growth factor, fibroblast growth factor, transforming growth factor and vascular endothelial growth factor. Furthermore, G. procumbens promoted in vitro wound healing and enhanced the migration and/or proliferation of human endothelial cells, fibroblasts, keratinocytes and mast cells cultured in diabetic conditions. Finally, G. procumbens promoted vascular formation in the diabetic mice. To the best of our knowledge, this is the first study that evaluates in vivo wound healing activities of G. procumbens and activation of cells involved in wound healing process in diabetic conditions. The findings that G. procumbens accelerates wound healing and activates cells involved in the wound healing process suggest that G. procumbens might be an effective alternative therapeutic option for nonhealing diabetic wounds.

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Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

International Journal of Molecular Sciences ◽

10.3390/ijms22084087 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4087

Author(s):

Maria Quitério ◽

Sandra Simões ◽

Andreia Ascenso ◽

Manuela Carvalheiro ◽

Ana Paula Leandro ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

In Vitro Release ◽

Peptide Hormone ◽

Plga Nanoparticles ◽

Wound Healing Process ◽

Target Area ◽

Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

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Jatropha Neopauciflora Pax Latex Exhibits Wound-Healing Effect in Normal and Diabetic Mice

Journal of Evidence-Based Integrative Medicine ◽

10.1177/2515690x20986762 ◽

2021 ◽

Vol 26 ◽

pp. 2515690X2098676

Author(s):

Ana Bertha Hernandez-Hernandez ◽

Francisco Javier Alarcon-Aguilar ◽

Mario Garcia-Lorenzana ◽

Marco Aurelio Rodriguez-Monroy ◽

Maria Margarita Canales-Martinez

Keyword(s):

Wound Healing ◽

Healing Process ◽

Wound Healing Process ◽

Diabetic Mice ◽

Wound Area ◽

Oral Infections ◽

Patients With Diabetes ◽

Exclusion Chromatography ◽

Wound Healing Effect ◽

Molecular Exclusion Chromatography

Jatropha neopauciflora is an endemic species of Mexico. Its latex is used to treat wounds, scarring, oral infections, and loose teeth. To date, there are no studies that validate at a morphological level a wound-healing use in diabetes. The present research aimed to evaluate the wound-healing capacity of the latex of J. neopauciflora in the skin of healthy and streptozotocin-induced diabetic mice. Also, a chemical analysis of the latex through molecular exclusion chromatography and HPLC were performed. Male mice ( Mus musculus) of 7-week-old CD1 strain were used. Groups of healthy and diabetic mice were formed. A longitudinal cut of 1 cm was performed on the depilated skin. All treatments were topically applied to the wound area twice a day for ten days. At the end of the experiments, the skin sections were obtained from the wound area and stained with Hematoxylin-Eosin. Then we counted the number of active fibroblasts in all the experimental groups. In normal mice, the latex accelerated the wound-healing process and decreased the number of active fibroblasts, similarly to Recoveron. In diabetic mice, the latex and Recoveron increased the number of active fibroblasts. In normal and diabetic mice, a thin and orderly epidermis was observed. Molecular exclusion chromatography exhibited 58 fractions, 14 of which were subjected to HPLC, to detect catechin, a flavonoid with antioxidant, antimicrobial, and anti-inflammatory properties. J. neopauciflora latex can be useful for wound treatment in patients with diabetes mellitus because it accelerates and promotes the wound-healing process.

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Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽

10.3390/molecules26092554 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2554

Author(s):

Marek Konop ◽

Anna K. Laskowska ◽

Mateusz Rybka ◽

Ewa Kłodzińska ◽

Dorota Sulejczak ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Diabetic Mice ◽

Full Thickness ◽

Skin Wound Healing ◽

Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

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Silk derived formulations for accelerated wound healing in diabetic mice

PeerJ ◽

10.7717/peerj.10232 ◽

2021 ◽

Vol 9 ◽

pp. e10232

Author(s):

Muniba Tariq ◽

Hafiz Muhammad Tahir ◽

Samima Asad Butt ◽

Shaukat Ali ◽

Asma Bashir Ahmad ◽

...

Keyword(s):

Wound Healing ◽

Silk Fibroin ◽

Chronic Wounds ◽

Histological Analysis ◽

Healing Process ◽

Aloe Vera ◽

Wound Contraction ◽

Wound Dressings ◽

Control Group ◽

Diabetic Mice

Background The present study aimed to prepare effective silk derived formulations in combination with plant extract (Aloe vera gel) to speed up the wound healing process in diabetic mice. Methods Diabetes was induced in albino mice by using alloxan monohydrate. After successful induction of diabetes in mice, excision wounds were created via biopsy puncture (6 mm). Wound healing effect of silk sericin (5%) and silk fibroin (5%) individually and in combination with 5% Aloe vera gel was evaluated by determining the percent wound contraction, healing time and histological analysis. Results The results indicated that the best biocompatible silk combination was of 5% silk fibroin and 5% Aloe vera gel in which wounds were healed in 13 days with wound contraction: 98.33 ± 0.80%. In contrast, the wound of the control group (polyfax) healed in 19 day shaving 98.5 ± 0.67% contraction. Histological analysis revealed that the wounds which were treated with silk formulations exhibited an increased growth of blood vessels, collagen fibers, and much reduced inflammation. Conclusion It can be concluded that a combination of Bombyx mori silk and Aloe vera gel is a natural biomaterial that can be utilized in wound dressings and to prepare more innovative silk based formulations for speedy recovery of chronic wounds.

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Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)

Nanomaterials ◽

10.3390/nano10061108 ◽

2020 ◽

Vol 10 (6) ◽

pp. 1108

Author(s):

Edorta Santos-Vizcaino ◽

Aiala Salvador ◽

Claudia Vairo ◽

Manoli Igartua ◽

Rosa Maria Hernandez ◽

...

Keyword(s):

Wound Healing ◽

Mechanism Of Action ◽

Healing Process ◽

Dermal Fibroblasts ◽

Control Group ◽

Promote Cell Proliferation ◽

Inflammatory Phase ◽

Inflammatory State ◽

Diabetic Wounds

Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal® Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing.

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Specific PKC βII inhibitor: one stone two birds in the treatment of diabetic foot ulcers

Bioscience Reports ◽

10.1042/bsr20171459 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 3

Author(s):

Sushant Kumar Das ◽

Yi Feng Yuan ◽

Mao Quan Li

Keyword(s):

Wound Healing ◽

Protein Kinase ◽

Peripheral Blood ◽

Wound Closure ◽

Type I Diabetes ◽

Healing Process ◽

Wound Healing Process ◽

Peripheral Blood Flow ◽

Type I ◽

Diabetic Mice

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.

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