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1.
J Nanobiotechnology ; 19(1): 304, 2021 Oct 02.
Article in English | MEDLINE | ID: mdl-34600530

ABSTRACT

BACKGROUND: Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated. RESULTS: In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine. CONCLUSIONS: HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing.


Subject(s)
Dermatologic Agents , Indoles , Nanoparticles , Peptides , Polymers , Wound Healing/drug effects , Animals , Cell Survival/drug effects , Dermatologic Agents/chemistry , Dermatologic Agents/pharmacology , Dermatologic Agents/toxicity , Disease Models, Animal , HaCaT Cells , Humans , Indoles/chemistry , Indoles/toxicity , Male , Mice , Mice, Nude , Nanoparticles/chemistry , Nanoparticles/toxicity , Peptides/chemistry , Peptides/pharmacology , Peptides/toxicity , Polymers/chemistry , Polymers/toxicity , RAW 264.7 Cells , Rats, Sprague-Dawley , Skin/drug effects , Skin/injuries , Swine
2.
Toxicology ; 458: 152840, 2021 06 30.
Article in English | MEDLINE | ID: mdl-34175381

ABSTRACT

Methotrexate (MTX) is one of the most effective and widely used drugs in the management of autoimmune and dermatological diseases. Rheumatoid arthritis and psoriasis patients who are under long term MTX-therapy are at high risk of developing a liver injury. Accumulation of intracellular MTX-polyglutamate (MTX-PG), a metabolite of MTX triggers oxidative stress, inflammation, steatosis, fibrosis, and apoptosis in hepatocytes. MTX-PG causes oxidative stress in the liver by inducing lipid peroxidation thereby releasing reactive oxygen species and suppressing antioxidant response elements. MTX-PG induces several pro-inflammatory signaling pathways and cytokines such as tumor necrosis factor-α, nuclear factor kappa B and interleukin 6 (IL-6), IL- ß1, IL-12. MTX-PG depletes hepatic folate level and decreases RNA and DNA synthesis leading to hepatocyte death. MTX-PG inhibits 5-aminoimidazole-4-carboxamide ribonucleotide transformylase enzyme and thereby causes accumulation of intracellular adenosine, which causes activation of hepatic stellate cells, extracellular matrix accumulation and hepatic fibrosis. MTX-PG induces hepatocytes apoptosis by activation of caspase 3 via the intrinsic pathway. Clinically, aggravation of underlying fatty liver to non-alcoholic steatohepatitis with fibrosis seems to be an important mechanism of liver injury in MTX-treated RA patients. Therefore, there is a need for monitoring liver injury in RA, psoriatic and cancer patients with NAFLD and fibrosis risk factors during MTX treatment. This review summarizes the possible molecular mechanism of MTX-induced hepatotoxicity. It may pave the way for early detection of liver injury and develop novel strategies for treating MTX mediated hepatotoxicity.


Subject(s)
Antirheumatic Agents/toxicity , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/therapy , Dermatologic Agents/toxicity , Methotrexate/toxicity , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Dermatologic Agents/adverse effects , Dermatologic Agents/therapeutic use , Humans , Methotrexate/adverse effects , Methotrexate/therapeutic use , Psoriasis/complications , Psoriasis/drug therapy
3.
FASEB J ; 35(5): e21574, 2021 05.
Article in English | MEDLINE | ID: mdl-33855746

ABSTRACT

Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG-deficient (Flg-/- ) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics on Flg-/- mice with calcipotriol (CPT)-induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generate Flg-/- mice and applied CPT to produce AD-like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin of Flg-/- mice to establish the AD-like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT-induced dermatitis in Flg-/- mice was more severer than that of wild-type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3+ T cells), and inflammatory cytokine expression (interleukin (IL)-4, IL-6, IL-13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation in Flg-/- mice with CPT-induced AD-like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT in Flg-/- mice could be utilized to search for drug targets in AD.


Subject(s)
Calcitriol/analogs & derivatives , Dermatitis, Atopic/pathology , Dermatologic Agents/toxicity , Disease Models, Animal , Inflammation/pathology , Intermediate Filament Proteins/physiology , Animals , Calcitriol/toxicity , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/genetics , Dermatitis, Atopic/metabolism , Female , Filaggrin Proteins , Inflammation/etiology , Inflammation/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout
4.
Int J Mol Sci ; 21(17)2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32878208

ABSTRACT

Atopic dermatitis (AD) is a complex, often lifelong allergic disease with severe pruritus affecting around 10% of both humans and dogs. To investigate the role of mast cells (MCs) and MC-specific proteases on the immunopathogenesis of AD, a vitamin D3-analog (MC903) was used to induce clinical AD-like symptoms in c-kit-dependent MC-deficient Wsh-/- and the MC protease-deficient mMCP-4-/-, mMCP-6-/-, and CPA3-/- mouse strains. MC903-treatment on the ear lobe increased clinical scores and ear-thickening, along with increased MC and granulocyte infiltration and activity, as well as increased levels of interleukin 33 (IL-33) locally and thymic stromal lymphopoietin (TSLP) both locally and systemically. The MC-deficient Wsh-/- mice showed significantly increased clinical score and ear thickening albeit having lower ear tissue levels of IL-33 and TSLP as well as lower serum levels of TSLP as compared to the WT mice. In contrast, although having significantly increased IL-33 ear tissue levels the chymase-deficient mMCP-4-/- mice showed similar clinical score, ear thickening, and TSLP levels in ear tissue and serum as the WT mice, whereas mMCP-6 and CPA3 -deficient mice showed a slightly reduced ear thickening and granulocyte infiltration. Our results suggest that MCs promote and control the level of MC903-induced AD-like inflammation.


Subject(s)
Calcitriol/analogs & derivatives , Dermatitis, Atopic/immunology , Ear Diseases/prevention & control , Hypersensitivity/prevention & control , Inflammation/prevention & control , Mast Cells/immunology , Serine Endopeptidases/physiology , Animals , Calcitriol/toxicity , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Dermatologic Agents/toxicity , Ear Diseases/etiology , Ear Diseases/metabolism , Ear Diseases/pathology , Female , Hypersensitivity/etiology , Hypersensitivity/metabolism , Hypersensitivity/pathology , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout
5.
Int J Toxicol ; 39(2_suppl): 26S-58S, 2020 09.
Article in English | MEDLINE | ID: mdl-32975154

ABSTRACT

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 60 PEGylated alkyl glycerides. PEGylated alkyl glycerides are mono-, di-, and/or triglycerides that have been modified with ethylene glycol repeat units (in the starting material form as epoxide). Most of the PEGylated alkyl glycerides are reported to function as skin-conditioning agents or surfactants. The Panel reviewed the available animal and clinical data as well as data from the 1999 report for the 5 polyethylene glycol (PEG) glyceryl cocoates and the 2012 report of PEGylated oils, to determine the safety of these ingredients. The Panel concluded these ingredients are safe in the current practices of use and concentration when formulated to be nonirritating; this conclusion supersedes the 1999 conclusion issued on 5 PEG glyceryl cocoate ingredients.


Subject(s)
Dermatologic Agents/toxicity , Glycerides/toxicity , Polyethylene Glycols/toxicity , Surface-Active Agents/toxicity , Animals , Consumer Product Safety , Cosmetics , Dermatologic Agents/chemistry , Dermatologic Agents/pharmacokinetics , Glycerides/chemistry , Glycerides/pharmacokinetics , Humans , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Risk Assessment , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacokinetics , Toxicity Tests
6.
J Nanobiotechnology ; 18(1): 80, 2020 May 24.
Article in English | MEDLINE | ID: mdl-32448273

ABSTRACT

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT. RESULTS: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis. CONCLUSIONS: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.


Subject(s)
Betamethasone , Dermatologic Agents , Liposomes , Psoriasis , Tretinoin , Animals , Betamethasone/chemistry , Betamethasone/pharmacokinetics , Betamethasone/pharmacology , Cell Survival/drug effects , Cytokines/metabolism , Dermatologic Agents/chemistry , Dermatologic Agents/pharmacokinetics , Dermatologic Agents/pharmacology , Dermatologic Agents/toxicity , Disease Models, Animal , Gels , HaCaT Cells , Humans , Liposomes/chemistry , Liposomes/pharmacokinetics , Liposomes/pharmacology , Liposomes/toxicity , Mice, Inbred BALB C , Particle Size , Pliability , Psoriasis/drug therapy , Psoriasis/metabolism , Rats , Rats, Sprague-Dawley , Tretinoin/chemistry , Tretinoin/pharmacokinetics , Tretinoin/pharmacology
7.
Anat Rec (Hoboken) ; 303(6): 1642-1652, 2020 06.
Article in English | MEDLINE | ID: mdl-32421930

ABSTRACT

Laminin-332 is a basement membrane protein composed of three genetically distinct polypeptide chains that actively promote both skin epidermal cell adhesion and migration. Proteolytic fragments of the laminin γ2 chain stimulate migration and scattering of keratinocytes and cancer cells. Sulfur mustard (SM) is a bifunctional alkylating agent that induces separation of basal keratinocytes from the dermal-epidermal junction and invokes a strong inflammatory response leading to delayed wound repair. In the present studies, the role of laminin γ2 in SM-induced skin injury and wound repair was investigated using the mouse ear vesicant model. We found that laminin γ2 chain mRNA was preferentially upregulated in mouse ear skin exposed to SM. In situ hybridization confirmed overexpression of laminin γ2 transcript. Western blot analysis showed increased protein expression of the full-length proform of laminin γ2 and smaller processed fragments of laminin γ2 in skin exposed to SM. Dual immunofluorescence labeling indicated that laminin γ2 fragments are prevalent in suprabasal keratinocytes behind the leading edge in areas of hyperplasia in injured skin. In addition, co-expression of laminin γ2 and the senescent marker, p16-INK4a was found to overlap with the hyperplastic migratory epithelial sheet. This observation is similar to hypermotile keratinocytes reported in invasive carcinoma cells. Overall, our studies indicate that laminin γ2 is preferentially expressed in skin post SM exposure and that protein expression appears to become progressively more fragmented. The laminin γ2 fragments may play a role in regulating SM-induced skin wound repair. Anat Rec, 2020. © 2020 American Association for Anatomy.


Subject(s)
Dermatologic Agents/toxicity , Laminin/metabolism , Mustard Gas/toxicity , Skin/metabolism , Wound Healing/physiology , Animals , Cell Movement/physiology , Keratinocytes/drug effects , Keratinocytes/metabolism , Laminin/genetics , Mice , Skin/drug effects , Up-Regulation
9.
Vet Dermatol ; 30(6): 474-e140, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31608529

ABSTRACT

BACKGROUND: Many dermatological topicals are available for human use and may be toxic to dogs and cats. No epidemiological studies have been performed in the US population on the use of dermatological topical prescription drugs, and their toxicosis to dogs and cats. OBJECTIVES: Summarize the variety of dermatological topical prescriptions potentially used by pet owners in the United States (US), and describe the epidemiology of dog and cat exposures and toxicities. ANIMALS/SUBJECTS: A dataset of 10,170 individuals from the National Health and Nutrition Examination Survey (NHANES) representative of 311,065,381 US residents. There were 61,169 dog and cat cases with exposure to dermatological topicals from the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC) database. METHODS AND MATERIALS: Prescription medication data were analyzed from NHANES 2011-2014 survey respondents. The APCC database was searched for records of dermatological topical drug cases between January 2001 and January 2018. RESULTS: Prescription dermatological topical medications were used by 1.33 ± 0.21% of the US population. Dermatological topical products (177, veterinary and human) resulted in 61,169 exposure calls to the APCC. Clinical signs developed in 38% (22,910). A human-labelled product was involved in 15% (3,463) with 74% (2,545) involving a prescription product. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Pets in households with humans receiving dermatological prescription topicals may be at risk for toxicosis. Multiple human-labelled dermatological topicals can cause death or major illness to dogs and cats at low dosages. Increased public awareness, especially attention to home storage practices for human-labelled dermatological topicals, may reduce the risk of exposure and toxicosis to dogs and cats.


Subject(s)
Dermatologic Agents/toxicity , Pets , Poisoning/veterinary , Prescription Drugs/toxicity , Administration, Topical , Animals , Cats , Databases, Factual , Dogs , Female , Humans , Male , Surveys and Questionnaires , United States
11.
Curr Med Chem ; 26(12): 2147-2165, 2019.
Article in English | MEDLINE | ID: mdl-30033865

ABSTRACT

In recent years inorganic materials are largely present in products intended for health care. Literature gives many examples of inorganic materials used in many healthcare products, mainly in pharmaceutical field. Silver, zinc oxide, titanium oxide, iron oxide, gold, mesoporous silica, hydrotalcite-like compound and nanoclays are the most common inorganic materials used in nanosized form for different applications in the health field. Generally, these materials are employed to realize formulations for systemic use, often with the aim to perform a specific targeting to the pathological site. The nanometric dimensions are often preferred to obtain the cellular internalization when the target is localized in the intracellular space. Some materials are frequently used in topical formulations as rheological agents, adsorbents, mattifying agents, physical sunscreen (e.g. zinc oxide, titanium dioxide), and others. Recent studies highlighted that the use of nanosized inorganic materials can represent a risk for health. The very small dimension (nanometric) until a few years ago represented a fundamental requirement; however, it is currently held responsible for the inorganic material toxicity. This aspect is very important to be considered as actually numerous inorganic materials can be found in many products available in the market, often dedicated to infants and children. These materials are used without taking into account their dimensional properties with increased risk for the user/patient. This review deals with a deep analysis of current researches documenting the toxicity of nanometric inorganic materials especially those largely used in products available in the market.


Subject(s)
Nanostructures/toxicity , Cosmetics/chemistry , Dermatologic Agents/chemistry , Dermatologic Agents/toxicity , Humans , Nanostructures/chemistry , Oxidative Stress/drug effects , Silicon Dioxide/chemistry , Skin/drug effects , Skin/metabolism , Sunscreening Agents/chemistry , Sunscreening Agents/toxicity , Titanium/chemistry , Zinc Oxide/chemistry
12.
Histol Histopathol ; 34(7): 755-763, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30556579

ABSTRACT

Isotretinoin is an analogue of vitamin A and by suppressing the sebaceous glands it is often prescribed in cases of severe acne treatment. The treatment for the average patient is carried out during two to ten months. This study was designed to investigate liver structure, hepatic enzyme levels and the stress oxidative parameter after isotretinoin treatment during a similar period and using the dosages of 1 mg/kg and another one of 10 mg/kg in young male Wistar rats. We have analyzed the blood serum biochemical levels to determine hepatic function and lipid peroxidation, hepatic tissue levels of hepatic enzymes, histology and ultrastructure. The groups receiving 1 mg/kg were not altered after treatment. Their ultrastructure showed a metabolically more active organ after treatment with 10 mg/kg, in which there was an increase in the area occupied by mitochondria and rough reticulum in electron transmission images. The group that received 10 mg/kg also showed increased alkaline phosphatase, decreased high density lipoprotein and low density lipoprotein. The changes observed with the 10 mg/kg dose were not conclusive for liver damage, because of the lack of histological structural modifications and the few biochemical alterations. The 1 mg/kg dose showed a liver responding to some stimuli but without profound alterations. So, we confirm that the proposed protocol with 1mg/kg or 10 mg/kg isotretinoin did not cause important biochemical and histological disfunctions for male Wistar rat livers.


Subject(s)
Dermatologic Agents/toxicity , Isotretinoin/toxicity , Liver/drug effects , Animals , Humans , Lipid Peroxidation/drug effects , Lipoproteins, LDL/metabolism , Liver/cytology , Liver/ultrastructure , Male , Oxidative Stress , Rats , Rats, Wistar
13.
Am J Emerg Med ; 36(9): 1719.e3-1719.e4, 2018 09.
Article in English | MEDLINE | ID: mdl-29861373

ABSTRACT

We present the case of a woman in her 50s with past medical history significant for psoriasis treated with methotrexate on a stable dose for the past 20 years, diabetes mellitus and chronic kidney disease. In the setting of a long flight, dehydration and non steroidal anti-inflammatory drug consumption, the patient presented to the emergency department with oral mucositis and cutaneous erosions and ulcers of the psoriasis plaques. MTX levels were normal corroborated by three different measurements in 24 h. Initially the complete blood count tests were significant for macrocytic, thrombocytopenia (82.000 103/L) and impaired kidney function. The patient was diagnosed of acute methotrexate toxicity and started on intravenous folinic acid. In 24 h the patient developed severe pancytopenia. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10 days, the CBC improved to normal levels and the cutaneous lesions resolved.


Subject(s)
Dermatologic Agents/toxicity , Methotrexate/toxicity , Dermatologic Agents/therapeutic use , Female , Humans , Methotrexate/therapeutic use , Middle Aged , Psoriasis/drug therapy , Skin Ulcer/chemically induced , Stomatitis/chemically induced
14.
J Ethnopharmacol ; 224: 85-90, 2018 Oct 05.
Article in English | MEDLINE | ID: mdl-29807119

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia anthelmintica has been utilized conventionally as an ingredient in Ayurveda and traditional Uighur medicine for management of various skin ailments, and scientific data's have substantiated its use in treating vitiligo, dermatosis and leucoderma. The present investigation was focused to evaluate the antipsoriatic activity of V. anthelmintica fruit extracts and fractions. MATERIALS AND METHODS: Ointment containing dichloromethane (DCM) and methanol (MeOH) extracts at topical dose of 2.5% and 5% (w/w) was evaluated using mouse tail model of psoriasis. Bioactivity-guided fractionation (F1-F7) of most active extract was carried out and fractions were again subjected to mouse tail model. Further the activity of bioactive fraction was confirmed in HaCaT (human keratinocyte) cell line using MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay and its chemical characterization was done via gas chromatography mass spectrometry (GC-MS). RESULTS: The dichloromethane extract (5%, w/w) showed statistically significant (* p < 0.05) antipsoriatic activity (66.97 ±â€¯2.68%) with respect to control (25.45 ±â€¯1.80%) and equivalent to that of the standard drug, retino-A 0.05%, (72.47 ±â€¯2.14%) in terms of degree of orthokeratosis, whereas methanol extract (5%, w/w) showed significant (* p < 0.05) differentiation (45.86 ±â€¯2.02%) in comparison to the control group. Out of all fractions, F6 showed statistically significant (* p < 0.05) antipsoriatic activity (69.27 ±â€¯2.76%) with respect to control and equivalent to that of the standard. F6 (15.6-1000 µg/ml) showed dose-dependent inhibition of HaCaT cell lines proliferation which suggests keratinocyte modulating activity of V. anthelmintica. Chemical characterization of F6 revealed that essential fatty acids (i.e., linoleic acid, palmitic acid, oleic acid and stearic acid) formed the bulk of bioactive fraction. CONCLUSION: Ameliorative effect of V. anthelmintica in psoriasis might be attributed to the presence of essential fatty acids and thus corroborates its traditional use in the treatment of skin ailments.


Subject(s)
Dermatologic Agents/therapeutic use , Fatty Acids/therapeutic use , Fruit/chemistry , Plant Extracts/therapeutic use , Psoriasis/drug therapy , Vernonia , Animals , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Dermatologic Agents/toxicity , Fatty Acids/toxicity , Female , Humans , Male , Mice , Ointments , Plant Extracts/toxicity , Skin/drug effects , Skin Irritancy Tests
15.
Eur J Pharm Sci ; 120: 142-151, 2018 Jul 30.
Article in English | MEDLINE | ID: mdl-29684425

ABSTRACT

The aim of present study was to design and optimize 0.1% adapalene loaded nano-emulsion to improve the drug efficacy and increase its user compliance. Effect of type and concentration of surfactants was studied on size of 0.1% adapalene loaded nano-emulsion. Optimized formulation was then evaluated for particle size, polydispersity index, morphology, viscosity, and pH. Subsequently, 1% carbopol® 934 was incorporated to the optimized formulation for preparation of its gel form. The efficacy and safety of 0.1% adapalene loaded nano-emulsion gel was assessed compared to marketed gel containing 0.1% adapalene. In-vitro studies showed that adapalene permeation through the skin was negligible in both adapalene loaded nano-emulsion gel and adapalene marketed gel. Furthermore, drug distribution studies in skin indicated higher retention of adapalene in the dermis in adapalene loaded nano-emulsion gel compared with adapalene marketed gel. Antibacterial activity against Propionibacterium acnes showed that adapalene loaded nano-emulsion is effective in reducing minimum inhibitory concentration of the formulation in comparison with tea tree oil nano-emulsion, and pure tea tree oil. In vivo skin irritation studies showed absence of irritancy for adapalene loaded nano-emulsion gel. Also, blood and liver absorption of the drug, histological analysis of liver and liver enzyme activity of rats after 90 days' treatment were investigated. No drug was detected in blood/liver which in addition to an absence of any adverse effect on liver and enzymes showed the potential of adapalene loaded nano-emulsion gel as a novel carrier for topical delivery of adapalene.


Subject(s)
Adapalene/administration & dosage , Anti-Infective Agents, Local/administration & dosage , Dermatologic Agents/administration & dosage , Nanostructures , Propionibacterium acnes/drug effects , Skin Absorption , Skin/metabolism , Tea Tree Oil/administration & dosage , Adapalene/chemistry , Adapalene/metabolism , Adapalene/toxicity , Administration, Cutaneous , Animals , Anti-Infective Agents, Local/chemistry , Anti-Infective Agents, Local/metabolism , Anti-Infective Agents, Local/toxicity , Dermatologic Agents/chemistry , Dermatologic Agents/metabolism , Dermatologic Agents/toxicity , Drug Combinations , Drug Compounding , Emulsions , Gels , Hydrogen-Ion Concentration , Nanotechnology , Particle Size , Permeability , Propionibacterium acnes/growth & development , Rabbits , Surface-Active Agents/chemistry , Tea Tree Oil/chemistry , Tea Tree Oil/metabolism , Tea Tree Oil/toxicity , Technology, Pharmaceutical/methods , Viscosity
16.
Eur Ann Allergy Clin Immunol ; 50(6): 273-276, 2018 11.
Article in English | MEDLINE | ID: mdl-29384118

ABSTRACT

Summary: DRESS (drug reaction with eosinophilia and systemic symptoms) is a rare but potentially life-threatening disorder characterized by fever, skin eruption, haematological abnormalities and multi-organ dysfunction after drug exposure. The pathophysiology is thought to be related to interactions between culprit drugs, viral reactivation and T-lymphocytes activation. We report 4 paediatric patients with DRESS who were treated at our centre over the past 12 years. Most cases improved after corticosteroids. Other immunosuppressive medications were attempted in refractory cases with varied outcomes. Patient 3 was the first reported case that involved the use of infliximab, a TNF-α inhibitor, for DRESS. Although clinical efficacy was not observed for this one patient, a previous study demonstrated that patients with DRESS, disease progression and HHV-6 reactivation had elevated pre-treatment TNF- α and IL-6 levels. Further research is needed to explore the role of these cytokines in DRESS.


Subject(s)
Dermatologic Agents/toxicity , Drug Hypersensitivity Syndrome/drug therapy , Drug Hypersensitivity Syndrome/epidemiology , Eosinophilia/chemically induced , Infliximab/toxicity , Adolescent , Adrenal Cortex Hormones/therapeutic use , Child, Preschool , Drug Hypersensitivity Syndrome/diagnosis , Female , Hong Kong/epidemiology , Humans , Male , Skin Tests , Tumor Necrosis Factor-alpha/antagonists & inhibitors
17.
Toxicol In Vitro ; 45(Pt 3): 397-408, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28389280

ABSTRACT

In the context of developing a new natural product-based cosmetic, the in vitro efficacy and safety evaluations of a complex botanical mixture based on Eugenia dysenterica leaf hydroalcoholic extract (EDE) (2.5-1000µg/mL) were carried out. Chromatographic analysis demonstrated the presence of the tannin (ellagic acid) and flavonoids (quercetin and gallic acid) which characterize the EDE as a polyphenol-rich mixture. Using HFF-1 fibroblasts, it was shown that EDE promoted cell regeneration after UVA exposure. It also led to the inhibition of the collagenase, elastase and tyrosinase enzymes, which are involved in skin-related disorders. In terms of toxicological evaluation, the EDE was classified as non-phototoxic through the 3T3 Neutral Red Uptake Phototoxicity Test (OECD N° 432, 2004) and non-eye irritant by Bovine Corneal Opacity and Permeability (OECD N° 437, 2013) assay, in conjunction with corneal histomorphometric analysis. Furthermore, the EDE has no skin sensitization potential as demonstrated by a two-out-of-three prediction model [protein-binding/haptenization (OECD N° 442C, 2015), keratinocyte and dendritic cell activations]. In addition, it was shown that the EDE seems to be non-genotoxic through the cytokinesis-block micronucleus assay (OECD N° 487, 2014) using HepG2 cells. When considered together, these findings support the use of EDE botanical mixture in cosmetic/pharmaceutical products.


Subject(s)
Cosmetics/chemistry , Cosmetics/toxicity , Dermatologic Agents/chemistry , Dermatologic Agents/toxicity , Eugenia/chemistry , Eugenia/toxicity , Animals , Cattle , Cells, Cultured , Complex Mixtures , Consumer Product Safety , Cornea/drug effects , Dendritic Cells/drug effects , Dermatitis, Phototoxic , Humans , Interleukin-18/metabolism , Irritants/toxicity , Keratinocytes/drug effects , Mice , Micronucleus Tests , Plant Extracts/chemistry , Plant Extracts/toxicity , Plant Leaves/chemistry
18.
J Trop Pediatr ; 63(1): 65-69, 2017 02.
Article in English | MEDLINE | ID: mdl-27370817

ABSTRACT

Balms and oils containing terpenic compounds, such as camphor, menthol and eucalyptus, are potentially toxic, and numerous reports of adverse events stemming from their use in infants and young children have been published. During qualitative research on newborn practices in rural Cambodia, these products were found to be commonly applied to the skin of newborns and infants and available in most households. Parents and caregivers of infants in Cambodia and other settings where use of camphor- and menthol-containing products are common should be educated on the risks of these to prevent child morbidity and potential mortality.


Subject(s)
Camphor/toxicity , Complementary Therapies/statistics & numerical data , Dermatologic Agents/toxicity , Health Knowledge, Attitudes, Practice , Infant Care/methods , Maternal Behavior , Oils, Volatile/toxicity , Cambodia , Complementary Therapies/adverse effects , Female , Humans , Infant , Infant, Newborn , Male , Qualitative Research
19.
Biomed Pharmacother ; 84: 1156-1162, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27780146

ABSTRACT

The aim of present study was to determine the effect of newly formulated gels and suspensions of extractive Phytoconstituents of Woodfordia fructicosa flowers and Gardenia gummifera leaves by using UV Radiation induced psoriasis in rats. Both plants are traditionally claimed to be useful in treatment of number of skin diseases. However, there are no established scientific reports for their potential in psoriasis. Formulated Gels and Suspensions of ethanolic extract of both plants were tested for acute dermal and oral toxicity study respectively. The results of acute dermal toxicity at concentration 1% w/w and oral toxicity at dose 1000mg/kg showed that the gels and suspensions were safe. Psoriasis was induced in Wistar rats by espousing 10% area of total body by UV radiations. Anti-psoriatic activity was performed by applying 0.1% gel and orally at a dose 100mg/kg body weight in rats. Severity Index, histological study and biochemical estimation were analyzed. The results of our studies showed that the test formulations (Gels and Suspensions) of both plant extracts exhibited potential effect in anti-psoriatic activity.


Subject(s)
Dermatologic Agents/pharmacology , Plant Extracts/pharmacology , Psoriasis/prevention & control , Skin/drug effects , Ultraviolet Rays , Administration, Cutaneous , Administration, Oral , Animals , Dermatologic Agents/isolation & purification , Dermatologic Agents/toxicity , Disease Models, Animal , Ethanol/chemistry , Female , Gardenia , Gels , Hydroxyproline/metabolism , Male , Pharmaceutical Solutions , Phytotherapy , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Plants, Medicinal , Psoriasis/metabolism , Psoriasis/pathology , Rats, Wistar , Severity of Illness Index , Skin/metabolism , Skin/pathology , Solvents/chemistry , Woodfordia
20.
Indian J Pharmacol ; 48(5): 531-536, 2016.
Article in English | MEDLINE | ID: mdl-27721539

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the antipsoriatic activity of ethanolic extract of Woodfordia fruticosa flowers (EEWF) using a novel in vivo screening model. MATERIALS AND METHODS: For induction of psoriasis, 0.1 ml of prepared complete Freund's adjuvant (CFA) and formaldehyde mixture (1:10 ratio) was topically applied for 7 days on the dorsum surface of the skin of Swiss albino mice. Psoriasis severity index (PSI) was evaluated by phenotypic (redness, erythema, and scales) and histological features (epidermal thickness). Therapeutic effect of 0.05% and 0.1% (w/w) ointments of EEWF was evaluated after the induction of psoriasis. Ointments of EEWF flowers were applied once daily for 3 weeks, and antipsoriatic activity was evaluated by scoring the PSI and histological examination. RESULTS: We observed the phenotypic and histological features and found a progressive reduction (P < 0.05) in the severity of psoriatic lesions (redness, erythema, and scales) from day 7 to 21st day and decreased epidermal thickness in animals treated with 0.05% and 0.1% (w/w) ointments of EEWF. CONCLUSIONS: The results showed that 0.05% and 0.1% (w/w) ointments of EEWF have dose-dependent beneficial effects in CFA and formaldehyde-induced psoriasis. The present investigation revealed that W. fruticosa flowers possess potent antipsoriatic activity and can be used for psoriasis treatment.


Subject(s)
Dermatologic Agents/therapeutic use , Disease Models, Animal , Plant Extracts/therapeutic use , Psoriasis/drug therapy , Woodfordia , Animals , Dermatologic Agents/chemistry , Dermatologic Agents/toxicity , Ethanol , Female , Flavonoids/analysis , Flowers/chemistry , Formaldehyde , Freund's Adjuvant , Male , Mice , Phenols/analysis , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/toxicity , Psoriasis/chemically induced , Psoriasis/pathology , Skin/drug effects , Skin/pathology , Solvents , Toxicity Tests, Acute , Woodfordia/chemistry
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