scholarly journals Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1386
Author(s):  
Yuan-Shuo Hsueh ◽  
Yan-Jye Shyong ◽  
Hsiu-Ching Yu ◽  
Shu-Jhen Jheng ◽  
Shang-Wen Lin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wound ◽  
Plasma Concentrations ◽  
Physical Stability ◽  
Systemic Exposure ◽  
Topical Administration ◽  
Diabetic Mouse ◽  
Nanostructured Lipid Carrier ◽  
Wound Model ◽  
Gel Formulations

Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.

scholarly journals Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 287 ◽  
Author(s):  
Carmelo Puglia ◽  
Debora Santonocito ◽  
Carmine Ostacolo ◽  
Eduardo Maria Sommella ◽  
Pietro Campiglia ◽  
...  
Keyword(s):  
Physical Stability ◽  
Topical Administration ◽  
Diabetic Rats ◽  
Nanostructured Lipid Carrier ◽  
The Novel ◽  
Tnf Α ◽  
Mean Size ◽  
Retinal Distribution ◽  
Factor Α ◽  
Ophthalmic Formulation

The present work was aimed for the preparation of a stable nanostructured lipid carrier (NLC) system for the delivery of N-palmitoylethanolamide (PEA) to the back of the eye. PEA is an interesting natural compound showing anti-inflammatory and neuroprotective activities. The limits of PEA (poor solubility and high instability) justify its nanoencapsulation into drug delivery systems. Two different well-known techniques were compared to formulate NLC: the high shear homogenization technique (HSH) and the method based on a combination of HSH technique and ultrasonication (HSH/US). Nanoparticles were evaluated in relation to mean size, homogeneity, surface charge, and physical stability by Turbiscan technology. Retinal distribution of PEA was carried out in a rat eye after single instillation of PEA-NLC ophthalmic formulation. The novel formulation delivered remarkable levels of PEA to the retina. Lastly, topical administration of PEA-NLC ophthalmic formulation was able to significantly inhibits retinal tumor necrosis factor-α (TNF-α) levels in streptozotocin-induced diabetic rats. The present findings suggest that the novel ophthalmic formulation may be useful for the treatment of retinal diseases such as diabetic retinopathy. Clinical studies are in progress to evaluate this possibility.

scholarly journals EFFECT OF THYMOQUINONE ON WOUND HEALING IN ALLOXAN-INDUCED DIABETIC RATS

2017 ◽  
Vol 10 (9) ◽  
pp. 242 ◽  
Author(s):  
Ahmadi Yusmin ◽  
Norhayati Ahmad
Keyword(s):  
Wound Healing ◽  
Nigella Sativa ◽  
Antimicrobial Properties ◽  
Topical Administration ◽  
Diabetic Rats ◽  
Active Constituent ◽  
Antiangiogenic Effect ◽  
Inflammatory Phase ◽  
Wound Model ◽  
And Function

  Objective: Nigella sativa and its active constituent thymoquinone (TQ) have been extensively documented for its pharmacological values, but its application in wound healing in particular in a diabetic wound healing model is less documented.Methods: In our study, alloxan-induced diabetic rats were used as a chronic delayed wound model and topical administration of TQ 10% w/v were used to assess the role and function of TQ in wound healing through wound contraction and histological analysis.Results: Although statistically insignificant, we found out that TQ accelerated wound healing in post-wounding day 3 (inflammatory phase), whereas aggressively decelerating wound healing in post-wounding day 7 (proliferation phase). In addition, our histological analyses of wound granulation tissues at post-wounding day 14 substantiate our claim by showing that TQ treatment had delayed wound healing progression of the diabetic rats.Conclusions: Our study shows that TQ accelerates wound healing during the inflammatory phase; however, decelerate rapidly during the proliferation phase. We speculate the acceleration of wound healing during the inflammatory phase was due to its well-documented antioxidant, anti-inflammatory, and antimicrobial properties while its deceleration of wound healing during the proliferation phase was due to its well-documented antiangiogenic effect.

scholarly journals Curcumin-In-Deformable Liposomes-In-Chitosan-Hydrogel as a Novel Wound Dressing

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 8 ◽  
Author(s):  
Selenia Ternullo ◽  
Laura Victoria Schulte Werning ◽  
Ann Mari Holsæter ◽  
Nataša Škalko-Basnet
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Chronic Wound ◽  
Skin Penetration ◽  
The Novel ◽  
Chitosan Hydrogel ◽  
Wound Model ◽  
Skin Delivery ◽  
Poorly Soluble ◽  
Dermal Delivery

A liposomes-in-hydrogel system as an advanced wound dressing for dermal delivery of curcumin was proposed for improved chronic wound therapy. Curcumin, a multitargeting poorly soluble active substance with known beneficial properties for improved wound healing, was incorporated in deformable liposomes to overcome its poor solubility. Chitosan hydrogel served as a vehicle providing superior wound healing properties. The novel system should assure sustained skin delivery of curcumin, and increase its retention at the skin site, utilizing both curcumin and chitosan to improve the therapy outcome. To optimize the properties of the formulation and determine the effect of the liposomal charge on the hydrogel properties, curcumin-containing deformable liposomes (DLs) with neutral (NDLs), cationic (CDLs), and anionic (ADLs) surface properties were incorporated in chitosan hydrogel. The charged DLs affected the hydrogel’s hardness, cohesiveness, and adhesiveness. Importantly, the incorporation of DLs, regardless of their surface charge, in chitosan hydrogel did not decrease the system’s bioadhesion to human skin. Stability testing revealed that the incorporation of CDLs in hydrogel preserved hydrogel´s bioadhesiveness to a higher degree than both NDLs and ADLs. In addition, CDLs-in-hydrogel enabled the most sustained skin penetration of curcumin. The proposed formulation should be further evaluated in a chronic wound model.

scholarly journals An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4610
Author(s):  
Hye-Jin Lee ◽  
Moses Jeong ◽  
Young-Guk Na ◽  
Sung-Jin Kim ◽  
Hong-Ki Lee ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Double Emulsion ◽  
Average Diameter ◽  
Diabetic Rats ◽  
Wound Healing Process ◽  
Nanostructured Lipid Carrier

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

scholarly journals In Vivo Wound Healing and In Vitro Anti-Inflammatory Activity Evaluation of Phlomis russeliana Extract Gel Formulations

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2695
Author(s):  
Mehmet Evren Okur ◽  
Ayşe Esra Karadağ ◽  
Neslihan Üstündağ Okur ◽  
Yağmur Özhan ◽  
Hande Sipahi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Activity ◽  
Wound Model ◽  
Aerial Parts ◽  
Excisional Wound ◽  
Anti Inflammatory ◽  
Cell Culture Assay ◽  
Gel Formulations

The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH• assay showed IC50 = 0.89 mg/mL, and the ABTS• assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC–FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.

scholarly journals Formulation and Phisical Stability Testing of Chitosan Gel from Vaname Shrimp Shell (Litopenaeus Vannamei) with Carbopol 940 Gelling Agent

2019 ◽  
Vol 1 (3) ◽  
Author(s):  
Norisca Aliza Putriana ◽  
Taofik Rusdiana ◽  
M. Abdul Aziz Prakoso
Keyword(s):  
Wound Healing ◽  
Tissue Injury ◽  
Physical Stability ◽  
Gelling Agent ◽  
Stability Testing ◽  
Normal Anatomy ◽  
Shrimp Shell ◽  
Carbopol 940 ◽  
Gel Formulations ◽  
Chitosan Gel

Wound is defined as a disorder of normal anatomy and skin’s function that occurs as a result of tissue injury or patalogic process resulting in epithelium discontinuity, with or without lossing underlying connective tissue. The use of chitosan in medicine, especially in surgery, gives many advantages in terms of wound healing that stimulates hemostasis of cell. Chitosan gel is one of the alternative wound treatments that still needs improvement, especially in terms of the effectiveness of the formulation. In this study, the physical stability of chitosan gel formulations was tested in various concentration of carbopol 940 as a gelling agent i.e, 0,5%, 1% and 1,5%. The parameters observed during the physical stability testing of this gel research were pH, viscosity, spreadability, homogeneity, organoleptic and sineresis gel. The result of the physical stability testing of chitosan gel stored for 56 days showed that formula 1 has the best result according to all parameters. Formula 1 has pH 5,8-6,2 at 25oC and 40oC, the best organoleptic stability, viscosity shift 9% at 25oC and 13,8% at 40oC, spreadability shift 10,9% at 25oC and 14,4% at 40oC. The best chitosan gel formulation for physical stability testing is chitosan gel with carbopol 940 concentration of 0.5%Keywords: Wound, Chitosan gel, Physical Stability

Wound healing activity of Ipomoea batatas tubers (sweet potato)

2011 ◽  
Vol 1 (10) ◽  
pp. 403 ◽  
Author(s):  
Vandana Panda ◽  
Madhav Sonkamble ◽  
Swati Patil
Keyword(s):  
Wound Healing ◽  
Tensile Strength ◽  
Sweet Potato ◽  
Ipomoea Batatas ◽  
Excision Wound ◽  
Wound Model ◽  
Malondialdehyde Content ◽  
Gel Formulations ◽  
Incision Wound ◽  
Peel Extract

Background: Ipomoea batatas (L.) Lam. from the family Convolvulaceae is the world’s sixth largest food crop. The tubers of Ipomoea batatas commonly known as sweet potato are consumed as a vegetable globally. The tubers contain high levels of polyphenols such as anthocyanins and phenolic acids and vitamins A, B and C, which impart a potent antioxidant activity that can translate well to show wound healing effects. To check their effects on wound healing, the peels and peel bandage were tested on various injury models in rats in the present study.Methods: The methanolic extracts of the peels and peel bandage of Ipomoea batatas tubers (sweet potato) were screened for wound healing by excision and incision wound models on Wistar rats. Three types of gel formulations were prepared, viz., gel containing 3.0% (w/w) peel extract, gel containing 6.0% (w/w) peel extract and gel containing 10% (w/w) peel extract. Betadine (5% w/w povidone iodine cream) was used as a reference standard. In the incision wound model, Tensile strength of the skin was measured. Epithelization time, wound contraction, hydroxyproline content of the scab, and ascorbic acid and malondialdehyde content of the plasma were determined in the excision wound model.Results: In the incision wound model, high tensile strength of the wounded skin was observed in animals treated with the peel extract gels and the peel bandage when compared with wounded control animals. The increase in tensile strength indicates the promotion of collagen fibers and that the disrupted wound surfaces are being firmly knit by collagen. In the excision wound model, significant wound closure was observed on the 4th day in rats treated with all three gel formulations when compared with the wounded control rats. A significant increase in hydroxyproline and ascorbic acid content in the gel-treated animals and a significant decrease in malondialdehyde content in the animals treated with gel as well as peel bandage was observed when compared with the wounded control animals.Conclusion: It may be concluded that the peels of Ipomoea batatas tubers possess a potent wound healing activity, which may be due to an underlying antioxidant mechanism.Key Words: Sweet potato peels, excision wound, incision wound, wound healing

scholarly journals Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing

2021 ◽  
Vol 11 (3) ◽  
pp. 1164
Author(s):  
Jahaziel Gasperin-Bulbarela ◽  
Ana B. Castro-Ceseña ◽  
Tanya Camacho-Villegas ◽  
Pavel H. Lugo-Fabres ◽  
Nestor Emmanuel Díaz-Martínez ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Wound Healing ◽  
Transforming Growth Factor Beta ◽  
Calcium Alginate ◽  
Neutralizing Antibodies ◽  
Chronic Wounds ◽  
Transforming Growth Factor ◽  
Topical Administration ◽  
Wound Model

Hydrogels provide effective alternatives for drug delivery when therapeutics cannot be applied directly to a wound, or if adverse effects are associated with systemic administration. However, drug delivery vehicles need to be biocompatible and biodegradable and exhibit sufficient mechanical strength to withstand handling and different physiological conditions, such as those encountered during topical administration of a therapeutic. Wound healing can be divided into three phases stimulated by transforming growth factor-beta (TGF-β) and, subsequently, targeted therapeutics have been developed to inhibit this cytokine for the treatment of chronic wounds and to prevent scarring. In this study, the capacity of calcium alginate hydrogels plasticized with poly(ethylene glycol) methyl ether methacrylate (PEGMA) to deliver anti-TGF-β antibodies (1D11.16.8) to a wound was investigated in situ. Three levels of antibodies, 10, 50, and 100 μg, were loaded into calcium-alginate-PEGMA hydrogels and evaluated in an excisional wound model in mice. Hydrogels containing 50 and 100 μg 1D11.16.8 produced less inflammation, accompanied by a marked reduction in collagen deposition and cell infiltration. These findings demonstrate the capacity of calcium-alginate-PEGMA hydrogels to deliver larger proteins, such as antibodies, to the site of a wound.

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