RESUMO
Free amino acids constitute the largest portion (40%) of the natural moisturizing factor. Their level might decline and cause dry skin condition. The treatment strategy involves the replenishment of these components to the skin, and, to our knowledge, there are no reports that involve dermal delivery of free amino acids. The purpose of the current study was therefore to prepare and characterize different micro-emulsions, micro-emulsion-based hydrogels, and hydrophilic creams loaded with free amino acids for dermal delivery. Oil-in-water microemulsions were prepared using carefully selected formulation components. Poloxamer® 407 and carbopol® 934 were used to prepare the hydrogels. All the formulations were characterized for physico-chemical, permeation and cytotoxicity properties. The results showed that the prepared microemulsions had desired droplet size, size distribution, zeta potential, refractive index, and pH. In the gel preparations, the elastic properties prevailed over the viscous behavior. The hydrogels had non-Newtonian shear-thinning behavior with some thixotropic properties. The free amino acids permeated into the deeper layers of the stratum corneum from the microemulsions, and microemulsion-based hydrogels as compared to conventional hydrophilic cream. The hydrogels were more effective than the microemulsions to deliver the FAAs to the desired site of the skin in a sustained manner. Poloxamer-based hydrogel permeated into deeper skin layers than Carbopol-based hydrogel. Formulations prepared using standard free amino acids and those extracted and purified from oyster mushroom had similar characteristics. All the formulations were stable and safe to be applied topically. In conclusion, microemulsions and microemulsion-based hydrogels can be considered as safe carrier systems for dermal delivery of free amino acids.
Assuntos
Aminoácidos , Hidrogéis , Hidrogéis/química , Hidrogéis/metabolismo , Emulsões/química , Emulsões/metabolismo , Aminoácidos/metabolismo , Poloxâmero , Pele/metabolismo , Administração CutâneaRESUMO
We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2â¯× 5â¯mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.
Assuntos
Alopecia em Áreas , Piperidinas/uso terapêutico , Alopecia , Alopecia em Áreas/diagnóstico , Alopecia em Áreas/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Pirimidinas , Pirróis/efeitos adversosRESUMO
Although primary hyperhidrosis is a common disease, secondary symptomatic hyperhidrosis is rather rare. Primary hyperhidrosis is a complex neuropathic dysregulation with a genetic predisposition and is diagnosed when patients show pathologic sweating patterns and excessive sweating for at least 6 months and fulfill at least four of the following criteria: affected areas are axillae and/or palms and/or soles and/or forehead; symmetry; no night sweating; at least once a week; onset before the age of 25; positive family history; negative impact on daily activities. Frequently used therapies are topical aluminum salts and anticholinergics, iontophoresis in water, and intracutaneous botulinum toxin. Anticholinergics are also used as systemic treatment. Surgical procedures are used as a last result. Furthermore procedures using thermolysis have been developed.
Assuntos
Hiperidrose , Compostos de Alumínio , Axila , Toxinas Botulínicas Tipo A , Humanos , Hiperidrose/diagnóstico , Hiperidrose/tratamento farmacológico , Hiperidrose/etiologia , IontoforeseRESUMO
Various hair-related diseases, systemic dermatoses as well as parasitic diseases are treated via topical application of active substances. The density of hair follicles and the consequential special conditions for diffusion require specific galenic concepts that can vary considerably depending on the respective therapeutic purpose. Both the physicochemical properties of the active ingredient and the nature of the application area must be considered when choosing an appropriate galenic base. Highly relevant here are hairiness, scarring, hyperkeratosis and exoserosis. Low-viscosity bases and foams are often preferred because of their good spreadability. Packages with nozzle tip or comb-shaped dispensers are user-friendly and can significantly enhance patient adherence to topical treatment.
Assuntos
Administração Cutânea , Fármacos Dermatológicos/administração & dosagem , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/tratamento farmacológico , Dermatoses do Couro Cabeludo/diagnóstico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Psoriasis is known today as a Tcell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric-neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABAA receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application. OBJECTIVES: For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed. CONCLUSION: The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)-the so-called 12-3-cream. A twice daily use of the 12-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration-time profile) on human skin and clinical studies would be necessary.
Assuntos
Hidrato de Cloral/administração & dosagem , Toxidermias/diagnóstico , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Modelos Biológicos , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Linhagem Celular , Hidrato de Cloral/efeitos adversos , Simulação por Computador , Relação Dose-Resposta a Droga , Toxidermias/etiologia , Toxidermias/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Queratinócitos/patologia , Taxa de Depuração Metabólica , Prurido/metabolismo , Prurido/patologia , Psoríase/metabolismo , Psoríase/patologiaRESUMO
The combination of topical fungicide and glucocorticoids has been proven as a successful therapy of cutaneous mycoses with accompanying inflammatory reactions, particularly when used at an early stage. Various national and international therapeutic guidelines recommend this practice. In this context, two individually manufactured formulations have been developed and tested for stability: the combination of methylprednisolone aceponate-a topical glucocorticoid with the therapeutic index of 2.0-with clotrimazole and with ciclopirox olamine, respectively. This has been conducted in compliance with the requirements for quality controlled extemporaneous formulations and the legal framework of the German Pharmacy Working Regulations (Apothekenbetriebsordnung). There are now two formulations for clinical use that are microbiologically, physically, and chemically stable, which combine methylprednisolone aceponate-a glucocorticoid with a good risk-benefit ratio-with the broad-spectrum fungicides clotrimazole and, for the first time, ciclopirox olamine.
Assuntos
Antifúngicos/administração & dosagem , Clotrimazol/administração & dosagem , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Metilprednisolona/análogos & derivados , Piridonas/administração & dosagem , Administração Tópica , Ciclopirox , Fármacos Dermatológicos/administração & dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Medicina Baseada em Evidências , Humanos , Metilprednisolona/administração & dosagem , Resultado do TratamentoRESUMO
Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using hens egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.
Assuntos
Ceramidas/administração & dosagem , Sistemas de Liberação de Medicamentos , Isossorbida/química , Pele/metabolismo , Animais , Ceramidas/farmacocinética , Ceramidas/toxicidade , Química Farmacêutica/métodos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Coloides , Difusão , Emulsões , Humanos , Isossorbida/administração & dosagem , Lipídeos/químicaRESUMO
Epithelial senescence is a complex process depending on intrinsic as well as extrinsic factors (e.g., UV or IR light, tobacco smoke) and must be seen in the context of the aging process especially of the corium and the subcutis. Morphological alterations become apparent in the form of epithelial atrophy, structural changes within the basal membrane, and a decrease in cell count of melanocytes and Langerhans cells. Signs of cellular senescence are reduced proliferation of keratinocytes, cumulation of dysplastic keratinocytes, various mutations (e.g., c-Fos/c-Jun, STAT3, FoxO1), as well as multiple lipid or amino acid metabolic aberrations (e.g., production of advanced glycation endproducts). This causes functional changes within the physical (lipid deficiency, water distribution dysfunction, lack of hygroscopic substances), chemical (pH conditions, oxygen radicals), and immunological barrier. Prophylactically, barrier-protective care products, antioxidant substances (e.g., vitamin C, B3, E, polyphenols, flavonoids), sunscreen products/measurements, and retinoids are used. For correcting alterations in aged epidermis, chemical peelings (fruit acids, ß-hydroxy acid, trichloroacetic acid, phenolic compounds), non-ablative (IPL, PDL, Nd:YAG) as well as ablative (CO2, Erbium-YAG) light-assisted methods are used.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Epiderme/efeitos dos fármacos , Epiderme/fisiologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Envelhecimento/fisiologia , Epiderme/patologia , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Envelhecimento da Pele/patologiaRESUMO
The effect of the lipophilicity of a carrier on human skin penetration of an extremely lipophilic active model substance was evaluated by using Franz type diffusion cells. Oil-in-water model emulsions containing different amounts of the oily phase were prepared, and Myritol® PC (M-PC) was selected as lipophilic marker component of the oily phase. The penetrated amounts of the lipophilic model substance salicyloyl phytosphingosine (SP) were determined by high-performance liquid chromatography with ultraviolet detection, while M-PC was detected using gas chromatography coupled with mass spectrometry. It has been ascertained that the amount of the lipid phase within the emulsion influenced the penetration profile of the active ingredient SP. The emulsion containing the lowest proportion of the lipid phase provides the best conditions for SP penetration. Surprisingly, the penetration behavior of M-PC was influenced by the oily phase in the same way. Regarding the M-PC and the SP penetration profiles from each emulsion, a solvent drag mechanism can be assumed whereby M-PC acts as penetration enhancer. In conclusion, the penetration rate of the active ingredient SP and the marker component M-PC are in reverse proportion to the oil content of the formulations. The lipophilicity of SP and M-PC, their solubility and their thermodynamic activity within the vehicle could have an effect on their penetration behavior. Additionally, M-PC has the property to enhance the penetration rates of extremely lipophilic substances even at low concentrations.
Assuntos
Caprilatos/metabolismo , Pele/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Caprilatos/química , Química Farmacêutica , Emulsões , Humanos , Técnicas In Vitro , Absorção Cutânea , Esfingosina/química , ÁguaRESUMO
Numerous dermatoses are treated with topically applied substances. Planning, conception, implementation and monitoring of topical therapies are dermatological core competencies. This requires fundamental knowledge about the physicochemical structure of skin layers, especially the stratum corneum, as well as about the interaction of both the active substance and the vehicle system with the skin. Professional treatment also requires basic knowledge about pharmacokinetics and the special features of epicutaneous drug administration.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacocinética , Absorção Cutânea , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo , Pele/metabolismo , Administração Cutânea , Animais , Medicina Baseada em Evidências , Humanos , Taxa de Depuração Metabólica , Modelos Biológicos , Distribuição TecidualRESUMO
To provide effective and appropriate therapy, careful planning is necessary, or even mandatory. The therapeutic options have to be assessed with regard to the current state of knowledge about efficacy and safety as well as patient-specific individual factors. Planning should consider dosing scheme, combination of active substances and vehicles, safety control, off-label use if necessary, and include measures to insure patient compliance. This approach makes it possible to clearly explain the therapy with the patient, and therefore consolidates the acceptance of the therapy by patient and physician.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Planejamento de Assistência ao Paciente , Dermatopatias/tratamento farmacológico , Administração Cutânea , Quimioterapia Combinada/métodos , Medicina Baseada em Evidências , HumanosRESUMO
The change in the population's age structure in most industrial countries, as in Germany, requires geriatric medicine to play an increasingly important role. Dermatology also has to meet the new challenges by expert discussion and ethical considerations. The physiological aging process is influenced by intrinsic and extrinsic factors and causes a variety of morphological and functional alterations in the skin. Those alterations are the cause for an increasing prevalence of many dermatoses. Infections, wound healing disorders, inflammatory diseases, tumors and associated paraneoplastic syndromes are of particular importance. The structural and functional characteristics of aging skin in combination with the reduced mobility and declining cognitive abilities in elder patients require specific recommendations for skin protection as well as qualified advice about topical and systemic use of medications.
Assuntos
Envelhecimento da Pele/patologia , Envelhecimento da Pele/fisiologia , Pele/patologia , Pele/fisiopatologia , HumanosRESUMO
Professional use of topical treatment in dermatological practice requires not only knowledge about the pharmacological properties, efficacy, safety and pharmaceutical quality of a preparation, but also about its regulatory classification. The latter essentially determines the physician's prescription practice and therapeutic freedom. The regulatory framework with which one is confronted unfortunately lacks transparency. It regulates not only the prescribability and reimbursability of proprietary medicinal products and extemporaneous preparations, but also the obligation to give information as well as the details of liability of both the prescriber (physician) and the manufacturer (pharmaceutical company or pharmacist). The prescriber needs to be aware of to what extent the pharmacist has the possibility and even obligation to change the prescribed preparation. In some cases this can directly affect the therapeutic concept of the physician and even impair the effectiveness and safety of the chosen therapy.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Dermatologia/legislação & jurisprudência , Prescrições de Medicamentos/normas , Regulamentação Governamental , Legislação de Medicamentos , Administração Cutânea , AlemanhaRESUMO
A 38-year-old woman presented with recurrent episodes of urticaria after contact with water affecting the upper part of the body. We confirmed the diagnosis of aquagenic urticaria. Aquagenic urticaria is a rare form of contact urticaria with small wheals generally affecting the upper part of the body. It has to be distinguished from aquagenic pruritus. The pathogenetic mechanisms are not known in detail. Treatment with antihistamines, ultraviolet therapy or application of protective hydrophobic barrier creams could be effective.
Assuntos
Bandagens , Cetirizina/administração & dosagem , Urticária/diagnóstico , Urticária/terapia , Adulto , Antialérgicos/administração & dosagem , Diagnóstico Diferencial , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Humanos , Resultado do Tratamento , Urticária Crônica InduzidaRESUMO
Changes related to aging affect all layers of the skin and are influenced by both intrinsic conditions and extrinsic factors. The extent of the senescent changes can vary enormeously in seniors, so that an individual assessment is useful and often necessary. Of particular clinical importance are changes in the epidermis, which entail a complex reduction of the barrier function and a reduction in the compensatory capacity with regard to exogenous noxae. This results in increased susceptibility, especially toward infection and cancer. Against this background, a prophylactic strategy for the substitution of the physicochemical and thus also the microbiological barrier in the context of basic care is very important. In order to be able to implement these consistently, recommendations for preparations explicitly designed for aging skin as well as practical instructions for use are highly meaningful. The latter should take into account limitations regarding mobility as well as possible cognitive deficits of seniors. For this purpose, creams and suitable preparations in terms of viscosity and composition should be recommended. In order to facilitate implementation, written or pictorial recommendations for application as well as digital assistance systems can be used. Due to demographic developments in Germany and Europe, the clinical relevance of geriatric dermatology will significantly increase in the future.
Assuntos
Dermatologia , Envelhecimento da Pele , Alemanha , Europa (Continente)RESUMO
Due to the lipophilic properties of the uppermost skin layer of the stratum corneum (SC), it is highly challenging to attain therapeutic concentrations of active substances; hydrophilic drugs, in particular, penetrate poorly. The purpose of this study was the improvement of the topical bioavailability of the hydrophilic dipeptides L-carnosine and its related compound N-acetyl-L-carnosine. Different strategies were investigated. On the one hand, an enhancer molecule, 1,2-pentylene glycol (PG), was added to a standard preparation, and on the other hand, a microemulsion (ME-PG) system was developed. Both were compared to the standard formulation without an enhancer molecule. For all 3 preparations, the penetration of the peptides in ex vivo human skin was investigated. This allows statements to be made regarding dermal penetration, localization and distribution of the active substances in each skin layer as well as the influence of vehicle variations, in this case, the addition of PG or the incorporation of N-acetyl-L-carnosine in an ME-PG system. For L-carnosine and N-acetyl-L-carnosine, the use of the standard preparation with PG resulted in a significant increase of the substance within the SC. Approximately 6-fold and higher dipeptide concentrations in the SC and in the viable skin layers were detected at all experimental periods compared to the formulation without the enhancer molecule and the ME-PG. High concentrations of the compounds were found after a short period of time in the viable skin layers after applying the enhancer molecule, even in concentrations of 5%. The application of the colloidal carrier system did not lead to a higher penetration rate of N-acetyl-L-carnosine in comparison to both standard preparations, although it must be said that the microstructure of the investigated ME-PG might not have been optimal for the hydrophilic properties of the dipeptide.
Assuntos
Carnosina/análogos & derivados , Carnosina/farmacocinética , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Pele/metabolismo , Administração Cutânea , Disponibilidade Biológica , Carnosina/administração & dosagem , Carnosina/química , Emulsões/administração & dosagem , Emulsões/química , Excipientes/administração & dosagem , Excipientes/química , Glicóis/administração & dosagem , Glicóis/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Técnicas de Cultura de Órgãos , Pentanos/administração & dosagem , Pentanos/químicaRESUMO
BACKGROUND: Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. OBJECTIVES: To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). METHODS: In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. RESULTS: Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). CONCLUSIONS: Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles.
Assuntos
Epiderme/patologia , Folículo Piloso/patologia , Hidradenite Supurativa/patologia , Adulto , Feminino , Humanos , Hiperplasia/patologia , MasculinoRESUMO
The barrier function of the stratum corneum (SC) significantly determines the interaction of epicutaneously applied substances with the skin organ. Although the exact molecular processes are still unclear, it is undoubted that the intercellular lipid composition and order of the SC is significantly involved in this interaction. Topically substituted phases, especially those of lipophilic composition, seem to interact very intensely with lipid membranes; they can be integrated, form separate phases, or even permeate through the SC into the viable skin. The latter is not desired, especially in barrier-protective preparations with a lipophilic phase. The present paper investigates the penetration behavior of topically applied, DiI-labeled lipids into human ex vivo skin depending on the phase organization of different o/w emulsifiers compared to emulsifier-free preparations containing hydrogenated phosphatidylcholine by means of fluorescence indication. Results are presented for intact and defined damaged epidermal barrier. In addition, the washout effect based on skin samples treated by artificial watering after lipid incubation, and the influence of the phase transition temperature of the SC membrane were studied. The results show that in intact and damaged skin, the penetration depth of the lipids increases directly proportionally with the hydrophilic-lipophilic balance (HLB value), while the washout effect and the HLB value proved to be inversely related. An increase in penetration depth with higher HLB values was also apparent when the phase transition temperature of the physiological membranes was exceeded. Altogether, the results clearly demonstrate that the characteristics of the emulsifying phase of a preparation significantly determine the interaction of a substituted lipophilic phase with the SC. Especially bipolar lipids, like phosphatidylcholines, showed intradermal dispersion patterns which hint at an especially intense interaction with physiological membranes.