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1.
Skin Pharmacol Physiol ; 34(6): 337-350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34404045

RESUMO

BACKGROUND: The chronicity of psoriasis often requires continuous topical treatment. MATERIALS AND METHODS: Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. RESULTS: EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. CONCLUSION: The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis.


Assuntos
Fármacos Dermatológicos , Psoríase , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Método Duplo-Cego , Humanos , Óleos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
2.
PLoS One ; 16(7): e0254608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34252151

RESUMO

In this retrospective multicentric cohort study, we evaluate the potential benefits of a clinical decision support system (CDSS) for the automated detection of Acute kidney injury (AKI). A total of 80,389 cases, hospitalized from 2017 to 2019 at a tertiary care hospital (University of Leipzig Medical Center (ULMC)) and two primary care hospitals (Muldentalkliniken (MTL)) in Germany, were enrolled. AKI was defined and staged according to the Kidney disease: improving global outcomes (KDIGO) guidelines. Clinical and laboratory data was automatically collected from electronic patient records using the frameworks of the CDSS. In our cohort, we found an overall AKI incidence proportion of 12.1%. We identified 6,393/1,703/1,604 cases as AKI stage 1/2/3 (8.0%/2.1%/2.0%, respectively). Administrative coding with N17 (ICD-10-GM) was missing in 55.8% of all AKI cases with the potential for additional diagnosis related groups (DRG) reimbursement of 1,204,200 € in our study. AKI was associated with higher hospital mortality, increased length of hospitalisation and more frequent need of renal replacement therapy. A total of 19.1% of AKI cases (n = 1,848) showed progression to higher AKI stages (progressive AKI) during hospitalization. These cases presented with considerably longer hospitalization, higher rates of renal replacement therapy and increased mortality (p<0.001, respectively). Furthermore, progressive AKI was significantly associated with sepsis, shock, liver cirrhosis, myocardial infarction, and cardiac insufficiency. AKI, and especially its progression during hospitalization, is strongly associated with adverse outcomes. Our automated CDSS enables timely detection and bears potential to improve AKI outcomes, notably in cases of progressive AKI.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/patologia , Idoso , Progressão da Doença , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
JMIR Med Inform ; 9(6): e20407, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081013

RESUMO

BACKGROUND: Laboratory results are of central importance for clinical decision making. The time span between availability and review of results by clinicians is crucial to patient care. Clinical decision support systems (CDSS) are computational tools that can identify critical values automatically and help decrease treatment delay. OBJECTIVE: With this work, we aimed to implement and evaluate a CDSS that supports health care professionals and improves patient safety. In addition to our experiences, we also describe its main components in a general manner to make it applicable to a wide range of medical institutions and to empower colleagues to implement a similar system in their facilities. METHODS: Technical requirements must be taken into account before implementing a CDSS that performs laboratory diagnostics (labCDSS). These can be planned within the functional components of a reactive software agent, a computational framework for such a CDSS. RESULTS: We present AMPEL (Analysis and Reporting System for the Improvement of Patient Safety through Real-Time Integration of Laboratory Findings), a labCDSS that notifies health care professionals if a life-threatening medical condition is detected. We developed and implemented AMPEL at a university hospital and regional hospitals in Germany (University of Leipzig Medical Center and the Muldental Clinics in Grimma and Wurzen). It currently runs 5 different algorithms in parallel: hypokalemia, hypercalcemia, hyponatremia, hyperlactatemia, and acute kidney injury. CONCLUSIONS: AMPEL enables continuous surveillance of patients. The system is constantly being evaluated and extended and has the capacity for many more algorithms. We hope to encourage colleagues from other institutions to design and implement similar CDSS using the theory, specifications, and experiences described in this work.

4.
Skin Res Technol ; 27(2): 191-200, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32686864

RESUMO

BACKGROUND: The recommended amount of sunscreen by hand application (2 mg/cm2 ) is in reality not achieved, which decreases the homogeneity and thereby the effective sun protection factor (SPF). MATERIALS AND METHODS: The homogeneity of sunscreen applied by a newly developed spray applicator using an electrostatically charged aerosol, for which a hand rubbing of the formulation is not necessary, is evaluated. In vivo experiments were performed on the volar forearms of human volunteers using the spray applicator compared to the standardized hand application according to ISO 24444. RESULTS: The distribution homogeneity was assessed qualitatively using in vivo laser scanning microscopy and quantitatively by absorption spectroscopy after tape stripping and by the standard deviation of multiple spatially displaced reflectance measurements for non-invasive SPF determination below the minimal erythemal dose, which showed a significantly higher homogeneity by 20.9% after spray application compared to hand application. CONCLUSION: Non-invasive SPF determination of multiple spatially displaced reflectance measurements was proven to be a suitable method for the non-invasive determination of the sunscreen distribution homogeneity. Electrostatically charged spray application increased the sunscreen distribution homogeneity on the skin and can reduce the amount of overspray.


Assuntos
Protetores Solares , Raios Ultravioleta , Humanos , Pele , Análise Espectral , Fator de Proteção Solar , Raios Ultravioleta/efeitos adversos
5.
Sensors (Basel) ; 20(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937874

RESUMO

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.


Assuntos
Folículo Piloso/química , Microscopia Confocal , Força Próton-Motriz , Sulfonatos de Arila , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Oxazinas , Triazinas
6.
Skin Res Technol ; 26(4): 558-563, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31919922

RESUMO

BACKGROUND: The decontamination of the skin is indispensable if airborne particulate contaminants deposit on the skin surface. Skin washing can have adverse effects as by skin rubbing the particles can be transferred deeply into the hair follicles, where they can be entrapped for a period of more than 10 days. Thus, alternative skin decontamination strategies are necessary. MATERIALS AND METHODS: For imaging the contaminants in the skin, sodium fluorescein-labeled soot particles of submicron size (≈600 nm) were visualized using laser scanning microscopy. RESULTS: In the present ex vivo pilot study on porcine ear skin, it was shown that sodium fluorescein-labeled soot particles of submicron size (≈600 nm) could be efficiently removed from the skin with highly absorbent textile nanofiber material, whose efficacy could be further increased by spraying the contaminated skin area with the viscous fluid PEG-12 dimethicone before textile application. CONCLUSION: In case of skin contamination with particulates, the contact washing should be avoided due to rubbing particles deeply into the hair follicles, where they can accumulate for a long time and induce negative consequences. Efficient skin decontamination could include pretreatment of skin surface with the viscous fluid PEG-12 dimethicone and subsequent application of highly absorbent textile nanofiber material.


Assuntos
Descontaminação , Nanofibras , Material Particulado , Higiene da Pele , Têxteis , Animais , Dimetilpolisiloxanos , Microscopia Confocal , Material Particulado/análise , Projetos Piloto , Higiene da Pele/métodos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Suínos
7.
Eur J Pharm Biopharm ; 139: 93-100, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878519

RESUMO

Topical retinoids are frequently applied for therapeutic and cosmeceutical reasons although their bioavailability is low due to their chemical and photochemical instability. Moreover, skin irritation is a common side effect. Therefore, proretinal nanoparticles (PRN) as a novel formulation of topical retinoids, which are based on chitosan grafted with retinal through reversible linkage, were developed and their skin penetration behavior was studied. As nanoparticles preferably penetrate into the hair follicles, the follicular penetration depths of PRN at different time points were investigated. Moreover, the release capacity of the nanoparticulate system was studied using fluorescein as a model drug. Additionally, the concentration of retinal in the stratum corneum and in the hair follicles was quantified after application in particulate and non-particulate form. The results showed that the nanocarriers reached the infundibular area of the hair follicles, irrespective of the incubation time. The nanoparticles were able to release their model drug within the hair follicle. The retinal concentration delivered to the stratum corneum and the hair follicles was significantly higher when retinal was applied in the particulate form. In conclusion, the presented proretinal nanoparticle system may help to overcome the main problems of topical retinoid therapy, which are skin irritation, chemical and photochemical instability and low bioavailability, thus improving the topical retinoid therapy.


Assuntos
Portadores de Fármacos/química , Folículo Piloso/metabolismo , Pró-Fármacos/farmacocinética , Retinaldeído/farmacocinética , Absorção Cutânea , Administração Cutânea , Animais , Disponibilidade Biológica , Quitosana/química , Modelos Animais , Nanopartículas/química , Pró-Fármacos/administração & dosagem , Retinaldeído/administração & dosagem , Sus scrofa
8.
Skin Res Technol ; 25(3): 389-398, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30758884

RESUMO

BACKGROUND: Skin diseases can develop upon disadvantageous microclimate in relation to skin contact with textiles of supporting devices. Increased temperature, moisture, mechanical fracture, pressure, and inflammatory processes often occur mutually and enhance each other in their adverse effects. Therefore, the early prevention of skin irritations by improvement of microclimatic properties of skin in contact with supporting devices is important. MATERIALS AND METHODS: In this study, the microclimate under occlusion with polyester, cotton, chloroprene rubber, and silicone textiles, used for supporting devices, was analyzed by determining several characteristic physiologic skin parameters in vivo, including temperature, moisture, and transepidermal water loss (TEWL). This is achieved by comparing a miniaturized in vivo detection device with several established optical and sensory methods in vivo. RESULTS: A highly significant TEWL decrease was found after polyester, chloroprene rubber, and silicone application. The application of all materials showed highly significant decrease in skin surface temperature, with chloroprene rubber showing the lowest. Similarly, all materials showed highly significant increase in relative moisture, where the highest increase was found for chloroprene rubber and silicone and the lowest increase for cotton. The cutaneous carotenoid concentration of chloroprene rubber, silicone, and polyester decreased. A manipulation of the surface structure of the stratum corneum was recognized for all materials except for cotton by laser scanning microscopy. CONCLUSION: The skin parameters temperature, relative moisture, antioxidant status, and TEWL can effectively characterize the microclimatic environment during occlusion with medical supporting materials. These parameters could potentially be used to develop standardized testing procedures for material evaluation.


Assuntos
Fibra de Algodão/efeitos adversos , Neopreno/efeitos adversos , Poliésteres/efeitos adversos , Silicones/efeitos adversos , Fenômenos Fisiológicos da Pele , Perda Insensível de Água , Adulto , Água Corporal , Células Epidérmicas , Voluntários Saudáveis , Humanos , Microclima , Pessoa de Meia-Idade , Pele/citologia , Temperatura Cutânea
9.
Skin Pharmacol Physiol ; 32(2): 65-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30612131

RESUMO

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.


Assuntos
Antioxidantes/análise , Carotenoides/análise , Ovos/análise , Administração Cutânea , Animais , Galinhas , Armazenamento de Alimentos , Luz , Análise Espectral Raman , Temperatura
10.
Skin Pharmacol Physiol ; 31(6): 308-315, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30184523

RESUMO

Psoriasis is prone to relapses and requires long-term therapy that may induce a range of adverse effects; therefore, an efficient and early detection of relapses is desirable. In this study, photoacoustic imaging and confocal laser scanning microscopic (CLSM) methods were investigated for their suitability in psoriasis follow-up examinations. Using a high-resolution photoacoustic system, the vascular structures of 11 psoriatic patients and 6 healthy volunteers were investigated. No differences were detected with respect to the average vessel diameter and vasculature per unit volume in the tissue of healthy volunteers and non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were determined. The diameters of the dermal papillae of the healthy volunteers (0.074 ± 0.006 mm) revealed no significant difference when compared to non-lesional skin areas of psoriatic patients (0.079 ± 0.005 mm). The results obtained for the lesions in psoriatic patients showed a significant difference (Wilcoxon test, p = 0.028) between the diameters of the dermal papillae of the lesional skin areas (0.114 ± 0.012 mm) and the non-lesional skin areas (0.079 ± 0.005 mm). Thus, CLSM can be applied for monitoring psoriasis follow-up examinations.


Assuntos
Psoríase/diagnóstico por imagem , Pele/diagnóstico por imagem , Acústica , Adulto , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Psoríase/patologia , Psoríase/fisiopatologia , Pele/irrigação sanguínea , Pele/patologia
11.
Skin Pharmacol Physiol ; 31(2): 87-94, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29353285

RESUMO

BACKGROUND/AIMS: Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. METHODS: In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. RESULTS: The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. CONCLUSION: The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser.


Assuntos
Nanopartículas/química , Pele/química , Fuligem/química , Alérgenos/química , Animais , Descontaminação/métodos , Humanos , Lasers , Microscopia Confocal/métodos , Tamanho da Partícula , Pólen/química , Suínos
12.
J Biomed Opt ; 22(7): 76018, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28753693

RESUMO

Topical glucocorticoids (GC) are known to induce changes in human skin with the potential to develop skin atrophy. Here, atrophogenic effects and subsequent structural changes in the skin after topical application of GC were investigated in vivo. Sixteen healthy volunteers were topically treated daily on the forearms with clobetasol propionate, betamethasone dipropionate, and the petrolatum vehicle for 4 weeks. All treated skin areas and a nontreated control area were examined by ultrasound, optical coherence tomography, confocal laser scanning microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at baseline 1 day after last application and 1 week after last application. Investigated parameters included stratum corneum thickness, epidermal, and full skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm ratio, skin surface classification, relative collagen and elastin signal intensity, second-harmonic generation-to-autofluorescence aging index of dermis (SAAID), and the antioxidant status of the skin. A reduction in epidermal and dermal skin thickness was observed in GC treated as well as in vehicle-treated and untreated skin areas on the volar forearm. MPT analysis showed an increased epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a significant increase of SAAID after GC treatment indicating a restructuring or compression of collagen fibers clinically being observed as atrophic changes.


Assuntos
Betametasona/análogos & derivados , Clobetasol/farmacologia , Pele/efeitos dos fármacos , Administração Tópica , Betametasona/administração & dosagem , Betametasona/farmacologia , Clobetasol/administração & dosagem , Epiderme/efeitos dos fármacos , Glucocorticoides/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Vaselina/administração & dosagem , Vaselina/farmacologia
13.
Eur J Pharm Biopharm ; 116: 102-110, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28043865

RESUMO

An improvement of the penetration efficiency combined with the controlled release of actives in the skin can facilitate the medical treatment of skin diseases immensely. Dexamethasone (Dx), a synthetic glucocorticoid, is frequently used for the treatment of inflammatory skin diseases. To investigate the penetration of nano-sized lipid particles (NLP) loaded with Dx in comparison to a commercially available base cream, different techniques were applied. Electron paramagnetic resonance (EPR) spectroscopy was used to monitor the penetration of Dx, which was covalently labeled with the spin probe 3-(Carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA). The penetration into hair follicles was studied using confocal laser scanning microscopy (CLSM) with curcumin-loaded NLP. The penetration of the vehicle was followed by confocal Raman microscopy (CRM). Penetration studies using excised porcine skin revealed a more than twofold higher penetration efficiency for DxPCA into the stratum corneum (SC) after 24h incubation compared to 4h incubation when loaded to the NLP, whereas when applied in the base cream, almost no further penetration was observed beyond 4h. The distribution of DxPCA within the SC was investigated by consecutive tape stripping. The release of DxPCA from the base cream after 24h in deeper SC layers and the viable epidermis was shown by EPR. For NLP, no release from the carrier was observed, although DxPCA was detectable in the skin after the complete SC was removed. This phenomenon can be explained by the penetration of the NLP into the hair follicles. However, penetration profiles measured by CRM indicate that NLP did not penetrate as deeply into the SC as the base cream formulation. In conclusion, NLP can improve the accumulation of Dx in the skin and provide a reservoir within the SC and in the follicular infundibula.


Assuntos
Dexametasona/administração & dosagem , Dexametasona/química , Lipídeos/administração & dosagem , Lipídeos/sangue , Nanopartículas/administração & dosagem , Nanopartículas/química , Pele/metabolismo , Animais , Curcumina/administração & dosagem , Curcumina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Orelha , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Epiderme/metabolismo , Excipientes/administração & dosagem , Excipientes/química , Glucocorticoides/administração & dosagem , Glucocorticoides/química , Folículo Piloso/metabolismo , Microscopia Confocal/métodos , Tamanho da Partícula , Absorção Cutânea , Suínos
14.
Eur J Pharm Biopharm ; 116: 12-16, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27693856

RESUMO

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles.


Assuntos
Dextranos/metabolismo , Portadores de Fármacos/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Folículo Piloso/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/metabolismo , Nanopartículas/metabolismo , Preparações Farmacêuticas/metabolismo , Soroalbumina Bovina/metabolismo , Pele/metabolismo , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos/métodos , Orelha , Fluoresceína-5-Isotiocianato/metabolismo , Corantes Fluorescentes/metabolismo , Absorção Cutânea/fisiologia , Suínos
15.
J Control Release ; 246: 174-182, 2017 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-27641832

RESUMO

More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle.


Assuntos
Preparações de Ação Retardada/química , Ouro/química , Nanopartículas/química , Preparações Farmacêuticas/administração & dosagem , Soroalbumina Bovina/química , Administração Cutânea , Animais , Bovinos , Preparações de Ação Retardada/metabolismo , Sistemas de Liberação de Medicamentos , Ouro/metabolismo , Folículo Piloso/metabolismo , Humanos , Raios Infravermelhos , Nanopartículas/metabolismo , Nanopartículas/ultraestrutura , Peptídeo Hidrolases/metabolismo , Soroalbumina Bovina/metabolismo , Absorção Cutânea , Suínos
16.
J Biomed Opt ; 21(5): 55004, 2016 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-27232593

RESUMO

The increased ability of TMX-202 (derivative of imiquimod) to penetrate the intact stratum corneum (SC) and the follicular orifices of porcine ear skin was shown ex vivo using confocal Raman microscopy and laser scanning microscopy. Moreover, to assess whether TMX-202 is able to reach the immune cells, Langerhans cells extracted from pretreated human skin were investigated ex vivo using confocal Raman microscopy combined with multivariate statistical methods. Tracking the Raman peak of dimethyl sulfoxide centered at 690 cm(−1), the absorption of TMX-202 containing formulation by Langerhans cells was shown. To answer the question whether the TMX-202 active ingredient is able to reach Langerhans cells, the attraction of immune cells to TMX-202 containing formulation treated skin was measured in the in vivo rodent model Mastomys coucha. The results show that TMX-202 active ingredient is able to reach Langerhans cells after penetrating through the intact skin and subsequently attract immune cells. Both the intercellular/transcellular as well as the follicular pathways allow the penetration through the intact barrier of the SC.


Assuntos
Adenina/análogos & derivados , Glicerofosfolipídeos/farmacologia , Células de Langerhans/efeitos dos fármacos , Microscopia Confocal , Absorção Cutânea , Pele/metabolismo , Análise Espectral Raman , Adenina/farmacologia , Animais , Humanos , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Murinae , Pele/citologia , Suínos
17.
Skin Pharmacol Physiol ; 29(2): 71-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27027785

RESUMO

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms.


Assuntos
Alérgenos/metabolismo , Antígenos CD1/metabolismo , Corantes Fluorescentes/metabolismo , Glicoproteínas/metabolismo , Bases para Pomadas/metabolismo , Pólen/metabolismo , Administração Cutânea , Alérgenos/administração & dosagem , Antígenos CD1/administração & dosagem , Composição de Medicamentos , Corantes Fluorescentes/administração & dosagem , Glicoproteínas/administração & dosagem , Humanos , Lipídeos/administração & dosagem , Lipídeos/farmacocinética , Bases para Pomadas/administração & dosagem
18.
J Biomed Opt ; 20(5): 051013, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25467783

RESUMO

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Microscopia Confocal , Floroglucinol/análogos & derivados , Pele/efeitos dos fármacos , Terpenos/química , Administração Cutânea , Cosméticos/química , Humanos , Inflamação , Lipídeos/química , Pomadas , Floroglucinol/química , Pele/metabolismo
19.
J Biophotonics ; 8(5): 382-91, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24659472

RESUMO

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Gases em Plasma/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/uso terapêutico , Interações Medicamentosas , Exsudatos e Transudatos/efeitos dos fármacos , Feminino , Humanos , Úlcera da Perna/tratamento farmacológico , Úlcera da Perna/microbiologia , Úlcera da Perna/patologia , Úlcera da Perna/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/induzido quimicamente , Gases em Plasma/efeitos adversos , Gases em Plasma/uso terapêutico
20.
J Biophotonics ; 7(9): 735-43, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24639418

RESUMO

Resonance Raman spectroscopy and multi-photon tomography were used in vivo to analyse the influence of sun exposure on the cutaneous carotenoids and collagen/elastin fibers. Comparing Berlin (low sun exposure) and Monegasque (high sun exposure) volunteers, it could be demonstrated that extended sun exposure significantly reduces the cutaneous carotenoids and collagen/elastin concentration (p < 0.05). The tendency towards correlation (R(2) = 0.41) between the dermal collagen/elastin (SAAID) and carotenoids confirms the important role of antioxidants in the protection against sun-induced negative effects. The application of sunscreen was shown to be effective, protecting cutaneous carotenoids and collagen/elastin from being damaged subsequent to sun exposure.


Assuntos
Carotenoides/metabolismo , Colágeno/metabolismo , Elastina/metabolismo , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Protetores Solares/farmacologia , Adulto , Antioxidantes/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Análise Espectral Raman , Adulto Jovem
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