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1.
Pharm Res ; 37(10): 195, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944793

RESUMO

PURPOSE: Design imiquimod-loaded chitosan nanocapsules for transdermal delivery and evaluate the depth of imiquimod transdermal absorption as well as the kinetics of this absorption using Raman Microscopy, an innovative strategy to evaluate transdermal absorption. This nanovehicle included Compritol 888ATO®, a novel excipient for formulating nanosystems whose administration through the skin has not been studied until now. METHODS: Nanocapsules were made by solvent displacement method and their physicochemical properties was measured by DLS and laser-Doppler. For transdermal experiments, newborn pig skin was used. The Raman spectra were obtained using a laser excitation source at 532 nm and a 20/50X oil immersion objective. RESULTS: The designed nanocapsules, presented nanometric size (180 nm), a polydispersity index <0.2 and a zeta potential +17. The controlled release effect of Compritol was observed, with the finding that half of the drug was released at 24 h in comparison with control (p < 0.05). It was verified through Raman microscopy that imiquimod transdermal penetration is dynamic, the nanocapsules take around 50 min to penetrate the stratum corneum and 24 h after transdermal administration, the drug was in the inner layers of the skin. CONCLUSIONS: This study demonstrated the utility of Raman Microscopy to evaluate the drugs transdermal penetration of in the different layers of the skin. Graphical Abstract New imiquimod nanocapsules: evaluation of their skin absorption by Raman Microscopy and effect of the compritol 888ATO® in the imiquimod release profile.


Assuntos
Quitosana/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Ácidos Graxos/farmacocinética , Imiquimode/farmacocinética , Nanocápsulas/administração & dosagem , Pele/metabolismo , Administração Cutânea , Animais , Quitosana/administração & dosagem , Quitosana/química , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Imiquimode/administração & dosagem , Imiquimode/química , Nanocápsulas/química , Microscopia Óptica não Linear/métodos , Absorção Cutânea , Suínos
2.
Adv Exp Med Biol ; 1268: 381-385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918229

RESUMO

BACKGROUND: The rule of thumb "Fill up a handful of sunscreen and spread it all over your body" has been used in several sun safety campaigns. The intention was to increase the applied sunscreen to obtain a quantity of 2 mg/cm2 to all accessible skin. The present study is the first to investigate how this advice works in practice, evaluated by quantity of sunscreen applied and amount of covered skin. METHODS: Seventeen volunteers wearing swimwear were asked to "Fill up a handful and spread it all over your body." Before and after sunscreen application, the volunteers were photographed in black light. As sunscreen absorbs black light, the darkness of the skin increases with increasing amounts of applied sunscreen, making it possible to identify skin left without coverage. The sunscreen container was weighed before and after to quantify the amount of sunscreen applied. RESULTS: A median of 21% of the accessible skin was left completely without coverage. The 79% covered area was covered with a median of 1.12 mg/cm2, not the expected 2 mg/cm2. CONCLUSION: In practice, the advice "Fill up a handful of sunscreen and spread it all over your body" led to a better but still modest protection, compared to the intended effect.


Assuntos
Pele/metabolismo , Protetores Solares/administração & dosagem , Protetores Solares/análise , Administração Cutânea , Cor , Humanos , Protetores Solares/farmacocinética
3.
Yakugaku Zasshi ; 140(9): 1175-1183, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879249

RESUMO

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Polímeros , Adesivo Transdérmico , Adesividade , Administração Cutânea , Ácidos Decanoicos , Liberação Controlada de Fármacos , Miristatos , Fenilacetatos/administração & dosagem , Fenilacetatos/metabolismo , Propionatos/administração & dosagem , Propionatos/metabolismo , Absorção Cutânea , Solubilidade , Análise Espectral Raman
4.
Medicine (Baltimore) ; 99(37): e22159, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925777

RESUMO

BACKGROUND: Long-term use of corticosteroid ointment for external using or skin management products and cosmetics containing corticosteroid will produce a hormone-dependent effect on facial skin and destroy the barrier function of the skin. It is easy to cause repeated attacks of facial skin inflammation after drug withdrawal because corticosteroid hormones can cause the expression of inflammatory factors in the body, which has a serious impact on patients. The general treatment method is to stop using hormone drugs for psychotherapy and inform patients of the basic knowledge of hormone-dependent dermatitis and daily facial care, but the effect is not good. At present, non-steroidal ointment tacrolimus (a calcineurin inhibitor) is widely used in the treatment of hormone-dependent dermatitis. Tacrolimus ointment is effective for corticosteroid-dependent dermatitis, but adverse events can also occur. METHODS: We plan to searched all randomized controlled trials (RCTs) fortacrolimus ointment therapy of hormone-dependent dermatitis in: MEDLINE, PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Springer and Web of Science, China Biomedical Literature Database (CBM), China Science Journal Database (VIP database) and Wanfang Database, China National Knowledge Infrastructure (CNKI), without the limitation of publication status and language until September 1, 2020. The systematic review will also search will also search for identify publications, meeting minutes, and grey literature (including unpublished meeting articles). DISCUSSION: The systematic review mainly to access the safety and efficacy of tacrolimus ointment for hormone-dependent dermatitis (facial corticosteroid addiction dermatitis and facial steroid dermatitis). The results of our research will facilitate evidence-based management of patients with facial corticosteroid-dependent dermatitis and provide clinical advice on their treatment options. REGISTRATION: PROSPERO CRD42020171813.


Assuntos
Corticosteroides/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Erupção por Droga/tratamento farmacológico , Erupção por Droga/etiologia , Tacrolimo/uso terapêutico , Administração Cutânea , Corticosteroides/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Humanos , Pomadas , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Tacrolimo/administração & dosagem
5.
Orv Hetil ; 161(38): 1646-1651, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32924969

RESUMO

As the topical use of non-steroidal anti-inflammatory drugs (NSAIDs) has gained popularity recently, adverse reactions related to their application have also become more common. The authors present the case of a 49-year-old man, who used etofenamate gel to treat leg pain. Following sun exposure, haemorrhagic, atypical lesions appeared and after rapid spread of the symptoms, the patient was hospitalized. In the area of the etofenamate application as well as on both legs, arms, trunk and face, confluent, erythematous sero-papules and macules were found, along with petechiae on the oral mucosa. Splenomegaly and thrombocytopenia accompanied the skin symptoms, which prompted an oncohematological workup, and the patient was diagnosed with hairy cell leukaemia. Epicutaneous testing (ET) was performed and found a positive reaction to etofenamate gel as well wood tar, propylen glycol, fragrance mix I, methylisothiazolinone, benzoic acid and balsam of Peru. The lymphocyte transformation test (LTT) and CD69 expression were negative for etofenamate. Orv Hetil. 2020; 161(38): 1646-1651.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Ácido Flufenâmico/análogos & derivados , Leucemia de Células Pilosas/diagnóstico , Esplenomegalia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Administração Cutânea , Administração Tópica , Anti-Inflamatórios não Esteroides/administração & dosagem , Ácido Flufenâmico/administração & dosagem , Ácido Flufenâmico/efeitos adversos , Humanos , Leucemia de Células Pilosas/patologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Púrpura/induzido quimicamente
6.
Int J Nanomedicine ; 15: 5517-5526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801703

RESUMO

Introduction: Hypertension is a major health problem worldwide and is typically treated using oral drugs. However, the frequency of oral administration may result in poor patient compliance, and reduced bioavailability owing to the first-pass effect can also prove problematic. Methods: In this study, we developed a new transdermal-drug-delivery system (TDDS) for the treatment of hypertension using atenolol (ATE) based on poly(acrylic acid) (PAA)-decorated three-dimensional (3D) flower-like MoS2 nanoparticles (PAA-MoS2 NPs) that respond to NIR laser irradiation. The PAA-modified MoS2 NPs were synthesized and characterized using attenuated total reflection Fourier-transform infrared spectroscopy, X-ray diffraction measurements, scanning electron microscopy, transmission electron microscopy, dynamic light scattering, and the sedimentation equilibrium method. The drug-loading efficiency and photothermal conversion effect were also explored. Results: The results showed that the colloidally stable PAA-MoS2 NPs exhibited a high drug-loading capacity of 54.99% and high photothermal conversion ability. Further, the capacity of the PAA-MoS2 NPs for controlled release was explored using in vitro drug-release and skin-penetration studies. The drug-release percentage was 44.72 ± 1.04%, and skin penetration was enhanced by a factor of 1.85 in the laser-stimulated group. Sustained and controlled release by the developed TDDS were observed with laser stimulation. Moreover, in vivo erythema index analysis verified that the PAA-MoS2 NPs did not cause skin irritation. Discussion: Our findings demonstrate that PAA-MoS2 NPs can be used as a new carrier for transdermal drug delivery for the first time.


Assuntos
Anti-Hipertensivos/administração & dosagem , Atenolol/administração & dosagem , Dissulfetos/química , Sistemas de Liberação de Medicamentos/métodos , Molibdênio/química , Nanopartículas/administração & dosagem , Resinas Acrílicas/química , Administração Cutânea , Animais , Anti-Hipertensivos/farmacocinética , Atenolol/efeitos adversos , Atenolol/farmacocinética , Sistemas de Liberação de Medicamentos/efeitos adversos , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Eritema/induzido quimicamente , Humanos , Lasers , Masculino , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Coelhos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
7.
Int J Nanomedicine ; 15: 5629-5643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801706

RESUMO

Purpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.


Assuntos
Flavanonas/administração & dosagem , Nanopartículas/administração & dosagem , Fosfolipídeos/química , Administração Cutânea , Animais , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Lecitinas/química , Masculino , Nanopartículas/efeitos adversos , Nanopartículas/química , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
8.
Int J Nanomedicine ; 15: 5671-5685, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821096

RESUMO

Aim: The aim of the current work was to develop vardenafil hydrochloride (VRD)-loaded ethosome-derived invasomes as a possible transdermal system which could be used for patients suffering from pulmonary arterial hypertension. Methods: VRD-loaded ethosomes were developed at three concentrations of phosphatidylcholine (5, 10 and 15 mg/mL) and three percentages of ethanol (20%, 30% and 40%, v/v). The best achieved VRD-loaded ethosomes (ETH9) were optimized to invasomes via incorporation of terpenes (limonene, cineole and a 1:1 mixture) at three concentrations (0.5%, 1% and 2%, v/v). All systems were evaluated for vesicle size, zeta potential, drug entrapment efficiency (EE%), cumulative drug permeated percentages after 0.5hrs (Q0.5h) and 12hrs (Q12h) and steady-state flux (Jss). The optimized system (ETH9-INV8) was further characterized for morphology, histopathology and confocal laser scanning microscopy (CLSM). Physiologically based pharmacokinetic (PBPK) modeling was employed to estimate VRD pharmacokinetic parameters from the optimized transdermal system and an oral aqueous drug dispersion, in adults and geriatrics. Results: The optimized invasomal system (ETH9-INV8) was characterized with spherical vesicles (159.9 nm) possessing negative zeta potential (-20.3 mV), promising EE% (81.3%), low Q0.5h (25.4%), high Q12h (85.3%) and the largest steady-state flux (6.4 µg.cm-2h-1). Following a leave-on period of 12hrs in rats, it showed minor histopathologic changes. CLSM studies proved its ability to deeply permeate rat skin. Lower Cmax values, delayed Tmax estimates and greater AUC0-24h folds in adults and geriatrics (≈ 2.18 and 1.69, respectively) were estimated following the transdermal application of ETH9-INV8 system. Conclusion: ETH9-INV8 is a promising transdermal system for VRD.


Assuntos
Sistemas de Liberação de Medicamentos , Etanol/química , Geriatria , Modelos Biológicos , Dicloridrato de Vardenafila/administração & dosagem , Dicloridrato de Vardenafila/farmacocinética , Administração Cutânea , Animais , Lipossomos , Masculino , Microscopia Confocal , Tamanho da Partícula , Permeabilidade , Ratos Wistar , Absorção Cutânea , Eletricidade Estática
9.
Int J Nanomedicine ; 15: 4763-4778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753865

RESUMO

Introduction: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis. Methods: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out. Results: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of -26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1ß, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples. Conclusion: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.


Assuntos
Composição de Medicamentos , Géis/química , Imiquimode/uso terapêutico , Inflamação/tratamento farmacológico , Lipídeos/química , Metotrexato/uso terapêutico , Nanoestruturas/química , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Animais , Catalase/metabolismo , Citocinas/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Inflamação/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Nanoestruturas/ultraestrutura , Tamanho do Órgão , Superóxido Dismutase/metabolismo
10.
An Acad Bras Cienc ; 92(2): e20191073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32696844

RESUMO

The objectives of this study are to prepare a 5 wt% lidocaine/aspirin ionic liquid drug-loaded gelatin/polyvinyl alcohol composite film using a freeze-thaw procedure and to evaluate their physicochemical characteristics, in vitro drug release, and stability. Lidocaine/aspirin ionic liquid drugs can be prepared by an ion-pair reaction between the hydrochloride salts of lidocaine and the sodium salts of aspirin, which showed a significant change in their thermal properties when compared to those pure drugs. The results showed that a transdermal patch could feasibly be used in pharmaceutical transdermal patches with good physicochemical properties. A chemical interaction between the drug and polymer base was not found. Decomposition of the lidocaine/aspirin ionic liquid drug was found in the patch; however, the properties of the patch were not changed after drug loading. The patch controlled the drug release and showed good stability during the studied period of three months when kept at 4°C more than at ambient temperature and 45°C.


Assuntos
Líquidos Iônicos , Adesivo Transdérmico , Administração Cutânea , Aspirina , Gelatina , Lidocaína , Álcool de Polivinil
11.
AAPS PharmSciTech ; 21(5): 180, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601758

RESUMO

Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P Ë‚ 0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato/administração & dosagem , Adesivo Transdérmico , Terapia por Ultrassom , Administração Cutânea , Animais , Masculino , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea
12.
Am J Physiol Heart Circ Physiol ; 319(2): H271-H281, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559139

RESUMO

The purpose of this study was to investigate the effect of race and subclinical elevations in blood pressure (i.e., prehypertension) on cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation. We recruited participants who self-identified as either non-Hispanic black (n = 16) or non-Hispanic white (n = 16). Within each group, participants were subdivided as either normotensive (n = 8 per group) or prehypertensive (n = 8 per group). Each participant was instrumented with four intradermal microdialysis fibers: 1) control (lactated Ringer's), 2) 5% lidocaine (sensory nerve inhibition), 3) 20 mM Nω-nitro-l-arginine methyl ester (l-NAME) (NO synthase inhibition), and 4) lidocaine + l-NAME. Skin blood flow was assessed via laser-Doppler flowmetry, and each site underwent local heating from 33°C to 39°C. At the plateau, 20 mM l-NAME were infused at control and lidocaine sites to quantify NO-dependent vasodilation. Maximal vasodilation was induced via 54 mM sodium nitroprusside and local heating to 43°C. Data are means ± SD. Sensory nerve-mediated cutaneous vasodilation was reduced in prehypertensive non-Hispanic white (34 ± 7%) and both non-Hispanic black groups (normotensive, 20 ± 9%, prehypertensive, 24 ± 15%) relative to normotensive non-Hispanic whites (54 ± 12%). NO-dependent vasodilation was also reduced in prehypertensive non-Hispanic white (41 ± 7%) and both non-Hispanic black groups (normotensive, 44 ± 7%, prehypertensive, 19 ± 7%) relative to normotensive non-Hispanic whites (60 ± 11%). The decrease in NO-dependent vasodilation in prehypertensive non-Hispanic blacks was further reduced relative to all other groups. These data suggest subclinical increases in blood pressure adversely affect sensory-mediated and NO-dependent vasodilation in both non-Hispanic blacks and whites.NEW & NOTEWORTHY Overt hypertension is known to reduce cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation, but the effect of subclinical increases in blood pressure (i.e., prehypertension) is unknown. The combined effect of race and prehypertension is also unknown. In this study, we found that prehypertension reduces cutaneous sensory nerve-mediated and NO-dependent vasodilation in both non-Hispanic white and black populations, with the greatest reductions observed in prehypertensive non-Hispanic blacks.


Assuntos
Pressão Sanguínea , Vasos Sanguíneos/inervação , Vasos Sanguíneos/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Pré-Hipertensão/fisiopatologia , Células Receptoras Sensoriais , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adolescente , Adulto , Afro-Americanos , Anestésicos Locais/administração & dosagem , Vasos Sanguíneos/efeitos dos fármacos , Estudos de Casos e Controles , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Grupo com Ancestrais do Continente Europeu , Feminino , Georgia/epidemiologia , Humanos , Masculino , Microdiálise , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/etnologia , Pré-Hipertensão/metabolismo , Fatores Raciais , Células Receptoras Sensoriais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Adulto Jovem
13.
Diab Vasc Dis Res ; 17(3): 1479164120928303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538145

RESUMO

AIM: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes. METHODS: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging. RESULTS: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores. CONCLUSION: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Microcirculação , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Feminino , Antebraço , Humanos , Iontoforese , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Angioscopia Microscópica , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem
14.
Xenobiotica ; 50(11): 1341-1351, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32501166

RESUMO

The specialty amine catalyst 2,2'-dimorpholinodiethyl ether (DMDEE) is a high-production volume chemical used in the production of flexible foam, high-resilient molded foam, and in coatings and adhesives. The disposition and metabolism of [14C]DMDEE (20 or 200 mg/kg) were determined in male ane female rats and mice after oral and intravenous administration and dermal application. In male and female rats, following a single oral administration, [14C]DMDEE was well-absorbed and excreted rapidly and extensively via urine (75-93%) and some in feces (∼4-8%). The total radioactivity in tissues at 24 h and 72 h (males only) following oral administration was 8-10% and ∼4%, respectively, suggesting considerable tissue distribution. A moderate amount of the total tissue radioactivity in kidney and liver were unextractable suggesting covalent binding of [14C]DMDEE-derived products in tissue macromolecules. Absorption following a single dermal application in rats was significant (∼64%) with a similar disposition pattern to oral. The oral and dermal disposition of [14C]DMDEE in male and female mice was similar to rats. Urinary products of DMDEE identified were oxidative metabolism of the morpholine ring. Coadministration of DMDEE with nitrite in rats didn't produce the rodent carcinogen, N-nitrosomorpholine.


Assuntos
Aminas/metabolismo , Administração Cutânea , Administração Intravenosa , Administração Oral , Animais , Feminino , Fígado , Masculino , Camundongos , Camundongos Endogâmicos , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
16.
Am J Vet Res ; 81(7): 581-593, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32584185

RESUMO

OBJECTIVE: To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep. ANIMALS: 12 healthy pregnant ewes. PROCEDURES: Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning 1 hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 µg of fentanyl/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times. RESULTS: Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time.


Assuntos
Buprenorfina , Fentanila , Dor Pós-Operatória , Administração Cutânea , Analgésicos , Analgésicos Opioides , Animais , Feminino , Feto , Dor Pós-Operatória/veterinária , Gravidez , Ovinos
17.
Int J Nanomedicine ; 15: 3539-3550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547012

RESUMO

Background: Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed. Materials and Methods: DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments. Results: In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100-120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX. Conclusion: These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.


Assuntos
Metotrexato/administração & dosagem , Micelas , Administração Cutânea , Animais , Cátions , Bovinos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Metotrexato/química , Camundongos , Concentração Osmolar , Tamanho da Partícula , Fosfatidilcolinas/química , Espectroscopia de Prótons por Ressonância Magnética , Soroalbumina Bovina/química , Pele/efeitos dos fármacos , Eletricidade Estática
18.
J Biomed Nanotechnol ; 16(3): 304-314, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32493541

RESUMO

We propose that nanogels (HLGs) prepared by simply blending an epidermal growth factor (EGF)-loaded hyaluronan (HA)-based nanoformulation and poloxamers can be efficient transdermal drug carriers. In particular, due to the thermogelling behavior of poloxamer, when the HLGs, which are liquid at room temperature, are applied to the skin's surface, they form a gel at skin temperature. First, lipid-based nanoformulations (EGF-LNs) were fabricated by the lipid thin film method and then chemically conjugated with HA on the surface of the films to prepare EGF-loaded HA-based nanoformulations (EGF-HLNs). Both EGF-LNs and EGF-HLNs exhibited a uniform size and spherical lamellar structure. The EGF-HLN was added to a poloxamer solution to form EGF-HLG, which is a liquid at room temperature and a gel at skin temperature. HLGs have been shown to be able to deliver and permeate EGF well into the skin using both in vitro and in vivo systems, thus serving as an effective transdermal delivery system. In addition, it has been confirmed that this system could be a possible implantable drug carrier. Therefore, HLGs, which are uncomplicated and easily prepared, are expected to be easily used not only in the pharmaceutical field but also in the cosmetic field.


Assuntos
Nanogéis , Cicatrização , Administração Cutânea , Portadores de Fármacos , Fator de Crescimento Epidérmico , Pele
19.
Support Care Cancer ; 28(9): 3991-3993, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32514616

RESUMO

Stringent measures have been taken to contain COVID-19 spread, limiting access only for urgent visits, surgery procedures, or hospitalizations and using teledermatology services for non-urgent cases. Management of oncological patients affected by chemo-, immune-, and radiotherapy-related cutaneous and mucosal adverse events is a challenge. Firstly because of the differential diagnosis of cutaneous rash (e.g., drug-related rash or paraviral exanthema). Secondly, oncological patients can suffer from xerosis, pruritus, and mucositis that contribute to cutaneous and mucosal barrier lesions, thus becoming vulnerable site for viral or bacterial colonization. These lesions can also be aggravated by the use of protective mask and gloves. Here, we report also our results of a teledermatological survey on 87 oncological patients, where the health status of oncological patients referred to our dedicated clinic was assessed during the COVID-19 pandemic. Therefore, it is fundamental that oncological patients are followed up by their dermatologists even if the clinics are closed. Teledermatology represents a crucial means of communication. Patients can contact the dermatological staff by emails and telephone, 24 h a day, 7 days a week, for video calls and dermatological consultations.


Assuntos
Infecções por Coronavirus/prevenção & controle , Membrana Mucosa/patologia , Neoplasias/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pele/patologia , Distância Social , Administração Cutânea , Betacoronavirus , Erupção por Droga/diagnóstico , Exantema/patologia , Exantema/virologia , Humanos , Itália , Masculino , Prurido/patologia , Prurido/virologia , Inquéritos e Questionários , Telemedicina/métodos
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