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Moringa oleifera standardised aqueous leaf extract-loaded hydrocolloid film dressing: in vivo dermal safety and wound healing evaluation in STZ/HFD diabetic rat model

Chin CY, Ng PY, Ng SF

Drug Deliv Transl Res, 2019 04;9(2):453-468.
PMID: 29560587 DOI: 10.1007/s13346-018-0510-z

Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.

Matched MeSH terms: Skin/metabolism
Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer

Rehman K, Zulfakar MH

Pharm Res, 2017 01;34(1):36-48.
PMID: 27620176 DOI: 10.1007/s11095-016-2036-8

PURPOSE: To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis.
METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model.
RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer.
CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

Matched MeSH terms: Skin/metabolism
Fulltext Differential expression of the angiogenesis growth factors in psoriasis vulgaris

Liew SC, Das-Gupta E, Chakravarthi S, Wong SF, Lee N, Safdar N, et al.

BMC Res Notes, 2012;5:201.
PMID: 22537619 DOI: 10.1186/1756-0500-5-201

Angiogenesis has been reported to be one of the contributory factors to the pathogenesis of psoriasis vulgaris. This study aims to compare the expression of different angiogenesis growth factors namely (1) the vascular endothelial growth factor (VEGF) subfamily: A, B, C, D and placenta growth factor (PlGF); (2) nerve growth factor (NGF) and (3) von Willebrand factor (vWFr) in the skins of patients with psoriasis vulgaris and non-psoriatic volunteers.

Study site: Dermatology Department of Hospital Kuala Lumpur, Kuala Lumpur and Tuanku Ja’afar Hospital, Seremban, Malaysia

Matched MeSH terms: Skin/metabolism*
Effect of non-phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib

Tamilvanan S, Baskar R

Pharm Dev Technol, 2013 Jul-Aug;18(4):761-71.
PMID: 23668371 DOI: 10.3109/10837450.2011.586038

Celecoxib (CXB, 0.2 g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method.

Matched MeSH terms: Skin/metabolism
Carbopol 934, 940 and Ultrez 10 as viscosity modifiers of palm olein esters based nano-scaled emulsion containing ibuprofen

Abdullah GZ, Abdulkarim MF, Mallikarjun C, Mahdi ES, Basri M, Sattar MA, et al.

Pak J Pharm Sci, 2013 Jan;26(1):75-83.
PMID: 23261730

Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol ® resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol ® 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol ® 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol ® 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol ® 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study.

Matched MeSH terms: Skin/metabolism
Fulltext In vitro permeation and in vivo anti-inflammatory and analgesic properties of nanoscaled emulsions containing ibuprofen for topical delivery

Abdullah GZ, Abdulkarim MF, Salman IM, Ameer OZ, Yam MF, Mutee AF, et al.

Int J Nanomedicine, 2011;6:387-96.
PMID: 21499428 DOI: 10.2147/IJN.S14667

As a topical delivery system, a nanoscaled emulsion is considered a good carrier of several active ingredients that convey several side effects upon oral administration, such as nonsteroidal anti-inflammatory drugs (NSAIDs).

Matched MeSH terms: Skin/metabolism
Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing

Xian LJ, Chowdhury SR, Bin Saim A, Idrus RB

Cytotherapy, 2015 Mar;17(3):293-300.
PMID: 25456581 DOI: 10.1016/j.jcyt.2014.10.005

Platelet-rich plasma (PRP) has been found to contain a high concentration of growth factors that are present during the process of healing. Studies conducted found that application of PRP accelerates wound healing. In this study, we characterized the skin cell suspension harvested using the co-isolation technique and evaluated the effects of PRP (10% and 20%, v/v) on co-cultured keratinocytes and fibroblasts in terms of wound healing.

Matched MeSH terms: Skin/metabolism
Fulltext Biocompatibility and toxicity of poly(vinyl alcohol)/N,O-carboxymethyl chitosan scaffold

Kamarul T, Krishnamurithy G, Salih ND, Ibrahim NS, Raghavendran HR, Suhaeb AR, et al.

ScientificWorldJournal, 2014;2014:905103.
PMID: 25298970 DOI: 10.1155/2014/905103

The in vivo biocompatibility and toxicity of PVA/NOCC scaffold were tested by comparing them with those of a biocompatible inert material HAM in a rat model. On Day 5, changes in the blood parameters of the PVA/NOCC-implanted rats were significantly higher than those of the control. The levels of potassium, creatinine, total protein, A/G, hemoglobulin, erythrocytes, WBC, and platelets were not significantly altered in the HAM-implanted rats, when compared with those in the control. On Day 10, an increase in potassium, urea, and GGT levels and a decrease in ALP, platelet, and eosinophil levels were noted in the PVA/NOCC-implanted rats, when compared with control. These changes were almost similar to those noted in the HAM-implanted rats, except for the unaltered potassium and increased neutrophil levels. On Day 15, the total protein, A/G, lymphocyte, monocyte, and eosinophil levels remained unaltered in the PVA/NOCC-implanted rats, whereas urea, A/G, WBC, lymphocyte, and monocyte levels remained unchanged in the HAM-implanted rats. Histology and immunohistochemistry analyses revealed inflammatory infiltration in the PVA/NOCC-implanted rats, but not in the HAM-implanted rats. Although a low toxic tissue response was observed in the PVA/NOCC-implanted rats, further studies are necessary to justify the use of this material in tissue engineering applications.

Matched MeSH terms: Skin/metabolism
Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar

Sideek MA, Teia A, Kopecki Z, Cowin AJ, Gibson MA

J Mol Histol, 2016 Feb;47(1):35-45.
PMID: 26644005 DOI: 10.1007/s10735-015-9645-0

We have recently shown that Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) has a single high-affinity binding site for fibroblast growth factor-2 (FGF-2) and that LTBP-2 blocks FGF-2 induced cell proliferation. Both proteins showed strong co-localisation within keloid skin from a single patient. In the current study, using confocal microscopy, we have investigated the distribution of the two proteins in normal and fibrotic skin samples including normal scar tissue, hypertrophic scars and keloids from multiple patients. Consistently, little staining for either protein was detected in normal adult skin and normal scar samples but extensive co-localisation of the two proteins was observed in multiple examples of hypertrophic scars and keloids. LTBP-2 and FGF-2 were co-localised to fine fibrous elements within the extracellular matrix identified as elastic fibres by immunostaining with anti-fibrillin-1 and anti-elastin antibodies. Furthermore, qPCR analysis of RNA samples from multiple patients confirmed dramatically increased expression of LTBP-2 and FGF-2, similar TGF-beta 1, in hypertrophic scar compared to normal skin and scar tissue. Overall the results suggest that elevated LTBP-2 may bind and sequester FGF-2 on elastic fibres in fibrotic tissues and modulate FGF-2's influence on the repair and healing processes.

Matched MeSH terms: Skin/metabolism*
Dexibuprofen loaded into nanoemulsion based gel for topical application - In vitro characterization and in vivo anti-inflammatory evaluation

Munir R, Khan IU, Kamal Y, Asghar S, Irfan M, Alshammari A, et al.

Colloids Surf B Biointerfaces, 2025 Mar;247:114407.
PMID: 39616935 DOI: 10.1016/j.colsurfb.2024.114407

Arthritic disease is one of the most common diseases in adults and a leading cause of joint degeneration. Dexibuprofen (DEX) is routinely used for the treatment of rheumatoid arthritis, acute postoperative pain, primary dysmenorrheal, and in lower back pain. However, it is poorly water soluble with compromised bioavailability, and hence has limited therapeutic activity. In order to overcome these issues, we studied the formulation and characterization of nanoemulsion based system i.e nanoemulgel of DEX. This study aimed to prepare topical nanoemulgel containing 2 % DEX and solubility-enhanced DEX via ternary inclusion complexation (DEX-SE-T) and to compare it with commercially available 5 % Ibuprofen gel as there is no topical formulation of DEX is available in the market currently. A pseudoternary phase diagram was constructed using the spontaneous water titration method. Blank and drug-loaded nanoemulgel were prepared using a high-speed homogenization method. All the formulations were evaluated in terms of particle size, pH, conductivity, viscosity, zeta potential, and ex vivo drug permeation. DEX loaded nanoemulgel yield enhanced in vitro skin permeation than the commercially available 5 % ibuprofen gel. The optimized nanoemulgel formulation (DEX-SE-T) was tested in in vivo anti-inflammatory models including cotton pellets-induced abdominal granuloma (chronic inflammation) and carrageenan-induced paw edema (acute inflammation). DEX-SE-T loaded nanoemulgel has improved in vivo anti-inflammatory activity as compared to ibuprofen gel. DEX-SE-T could be a promising option for effective topical treatment of inflammatory conditions.

Matched MeSH terms: Skin/metabolism
Treatment for diabetic ulcer wounds using a fern tannin optimized hydrogel formulation with antibacterial and antioxidative properties

Lai JC, Lai HY, Nalamolu KR, Ng SF

J Ethnopharmacol, 2016 08 02;189:277-89.
PMID: 27208868 DOI: 10.1016/j.jep.2016.05.032

ETHNOPHARMACOLOGICAL RELEVANCE: Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin.
AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds.
MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05).
RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis.
CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.

Matched MeSH terms: Skin/metabolism