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Photodynamic therapy (PDT) using methylene blue (MB) as a photosensitizer has emerged as an alternative treatment for skin cancers, such as squamous cell carcinoma (SCC). To increase the cutaneous penetration of the drug, some strategies are used, such as the association of nanocarriers and physical methods. Thus, herein we address the development of nanoparticles based on poly-Ɛ-caprolactone (PCL), optimized with the Box-Behnken factorial design, for topical application of MB associated with sonophoresis. The MB-nanoparticles were developed using the double emulsification-solvent evaporation technique and the optimized formulation resulted in an average size of 156.93 ± 8.27 nm, a polydispersion index of 0.11 ± 0.05, encapsulation efficiency of 94.22 ± 2.19% and zeta potential of -10.08 ± 1.12 mV. Morphological evaluation by scanning electron microscopy showed spherical nanoparticles. In vitro release studies show an initial burst compatible with the first-order mathematical model. The nanoparticle showed satisfactory generation of reactive oxygen species. The MTT assay was used to assess cytotoxicity and IC50; values of 79.84; 40.46; 22.37; 9.90 µM were obtained, respectively, for the MB-solution and the MB-nanoparticle without and with light irradiation after 2 h of incubation. Analysis using confocal microscopy showed high cellular uptake for the MB-nanoparticle. With regard to skin penetration, a higher concentration of MB was observed in the epidermis + dermis, corresponding to 9.81, 5.27 µg/cm2 in passive penetration and 24.31 and 23.81 µg/cm2 after sonophoresis, for solution-MB and nanoparticle-MB, respectively. To the best of our knowledge, this is the first report of MB encapsulation in PCL nanoparticles for application in skin cancer using PDT.

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Background: The taxonomic order Anura is composed of frogs and toads, with approximately 6,000 species worldwide, of which 900 species are found in Brazil. Rhinella marina, popularly known as "sapo-cururu," is the most commonly found frog in Brazil. Although most of these animals are found in research laboratories and zoos, they are increasingly being reared as pets. Therefore, sedation or anesthesia is often necessary for these animals to facilitate medical care, complementary examinations, or surgical procedures. However, there are only a few reports of anesthesia in frogs. Therefore, the present report aimed to describe the anesthetic protocol for femoral osteosynthetic surgery in an adult cane toad. Case: An adult cane toad presented with a history of difficulty in moving the left hindlimb and loss of limb movements. Radiography showed a simple, complete, transverse, and closed average shaft of the left femur and bone shaft fracture deviation. The animal was referred for an osteosynthetic surgery to stabilize the fracture. Animal restraint was performed using humidified gloves on the operating table. As premedication, ketamine, meloxicam, and morphine were administered, and general anesthesia was induced with isoflurane through a face mask. The anesthesia was maintained with isoflurane through a drip on the animal's back for cutaneous absorption. Lidocaine (2%) anesthetic gel was applied on the incision line to complement the somatic analgesia. The fracture was fixed using an intramedullary Kirschner pin. The heart rate was measured based on the beep of the arterial pulse using a Doppler ultrasonic device, respiratory rate was recorded by visual observation of the animal's respiratory motion, and body temperature was assessed using an esophageal digital thermometer - all of these remained stable during the procedure. Morphine, enrofloxacin, and meloxicam were administered postoperatively. The animal was discharged from the hospital seven days after the surgery, and 14 days later, the animal was deemed clinically stable with favorable wound healing. Discussion: Toads use their skin to breathe and maintain osmotic balance. Therefore, their skin is extremely sensitive to dehydration, requiring constant wetting. General anesthesia in amphibians is recommended for prolonged and painful procedures, as in the present case. Different anesthetics, analgesics, and associated drugs may be used. Ketamine is often used for chemical restraint in amphibians, and the induction and recovery times may vary due to sensitivity and drug resistance. Inhalational anesthesia with isoflurane may also be effective; in the present case, the anesthetic was administered using a mask placed on the frog's skin, without any irritation. Analgesia is essential for any animal, and amphibians have opioid receptors that may be used as targets of non-steroidal anti-inflammatory agents. As indicated for all species, the animal was monitored throughout the procedure. Assessment of heartbeat is the simplest way to monitor anesthesia using Doppler (on the heart or throat); in the present case, was placed on the axillary artery for clear auscultation. In addition, other parameters, such as temperature and primary respiratory movements, were monitored. Anesthetic recovery can take hours or even days, whereas excretion depends on the metabolic rate of each animal. In the present case, recovery was observed 4 h after completion of the procedure, using fresh water on the animal's body to accelerate recovery, as indicated in the literature. This case demonstrated that anesthesia and medications used for anesthesia induction, maintenance, and recovery are safe in toads. For cane toads, during femoral osteosynthesis, this anesthetic procedure has never been described previously in the literature. Finally, such information can aid veterinarians in performing safe and adequate analgesic and anesthetic procedures for the wellbeing of animals.

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Purpose:To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model.Methods:An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05).Results:Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751).Conclusion:The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.(AU)

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Abstract Purpose: To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. Methods: An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). Results: Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). Conclusion: The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.

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A restauração da barreira cutânea é o primeiro passo para o controle da dermatite atópica (DA) em todas as suas formas. O tratamento da DA grave ou refratária em crianças apresenta alguns desafios, devido principalmente aos efeitos colaterais das drogas imunossupressoras. Como alternativa, as técnicas "Wet Wraps" e "Soak and Smear" são intervenções seguras e eficazes em casos em que a xerose é fator determinante de agravamento da doença. Relata-se o caso de um menino de 5 anos com DA grave (SCORAD = 54) não controlada, com prurido intenso e distúrbio do sono. Houve tratamento prévio com corticoide tópico e sistêmico, diversos emolientes, uso repetido de antibióticos tópicos e sistêmicos, e restrição de leite de vaca, sem resultado. As comorbidades incluíam rinite alérgica (sensibilizado para ovo, leite, epitélio de cão e ácaros) e transtorno do espectro autista. Foi realizado tratamento tópico com ácido fusídico e corticoide de média potência, além de otimização das técnicas de restauração de barreira cutânea. Após um mês, o paciente retornou com melhora quase completa das lesões, SCORAD de 17 (leve), referindo intensa melhora na qualidade de vida, com resolução do distúrbio do sono. Este caso demonstrou a efetividade das técnicas "Wet Wraps" e "Soak and Smear" em criança com DA grave. A boa adesão e a correta execução são fundamentais para o resultado, ressaltando a importância da atenção médica quanto à educação da equipe e dos pais sobre o tratamento. Essas técnicas são bem estudadas e podem ser realizadas como resgaste na DA grave, mesmo em crianças com alterações comportamentais, e, se adequadamente utilizadas, podem evitar a prescrição de imunossupressores.

Skin barrier repair is the first step to control all forms of atopic dermatitis (AD). Treatment of severe or refractory AD in children poses some challenges, mainly due to the side effects of immunosuppressive drugs. As an alternative treatment, "Wet Wraps" and "Soak and Smear" techniques are safe and effective interventions when xerosis is an aggravating factor of the disease. We report the case of a 5-year-old boy with severe AD (SCORAD = 54), showing severe pruritus and sleep disorder. Prior treatment involved topical and systemic corticosteroids, several emollients, repeated use of topical and systemic antibiotics, and restriction to cow's milk, without any positive result. Comorbidities included allergic rhinitis (sensitized to egg, milk, dog epithelium and mites) and autism spectrum disorder. Topical treatment with fusidic acid and medium-potency corticoid was performed, in addition to optimization of skin barrier repair techniques. After one month, the patient returned with clinical improvement, SCORAD of 17 (mild), reporting a strong improvement in quality of life and no sleep disorder. This case demonstrates the effectiveness of the "Wet Wraps" and "Soak and Smear" techniques when applied to children with severe AD. Good adherence and correct execution are fundamental to outcomes, stressing the importance of medical care in the education of team and parents about the treatment. These techniques are well studied and can be performed as rescue therapy in severe AD, even in children with behavioral disorders, and, if properly used, may avoid prescription of immunosuppressants.

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Abstract: Sensitive skin is a condition characterized by stinging, burning and itching sensations. The diagnosis, pathophysiology and treatment of sensitive skin are still under discussion. In the last years, studies on its epidemiology have been performed, showing a high prevalence and impact on quality of life. Brazilian population was also considered in these studies. Cosmetics, climate changes and skin barrier impairment are the main factors that contribute for skin hyperreactivity. New studies are trying to bring new knowledge about the theme. This review will describe data on epidemiology, triggering factors, pathophysiology, diagnosis and treatment.

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ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

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A via tópica de entrega de medicamentos é essencial na dermatologia. O drug delivery otimiza a penetração de medicamentos e, realizado por lasers, ocorre de forma uniforme e controlada. O grau de evidência do drug delivery está em investigação para diversos medicamentos. Além disso, a técnica é excelente associação com a atuação dos lasers para rejuvenescimento e para tratamento de doenças dermatológicas. Conclusão: O uso de lasers para drug delivery é promissor: enquanto algumas substâncias possuem estudos clínicos que permitem indicar sua realização, outras necessitam de estudos controlados e com maior tempo de seguimento para sua avaliação.

The topical route for the delivery of drugs is essential in dermatology: it optimizes the penetration of medicaments, and when performed with the assistance of lasers, it takes place in a uniform and controlled manner. The degree of evidence of drug delivery is being investigated for many drugs. Moreover, the technique combines outstandingly with lasers for rejuvenation and treatment of skin diseases. It is therefore possible to conclude that the use of lasers for drug delivery is promising. While there are clinical studies on some substances that allow their indication and use, others require further controlled analyses, with longer follow-up periods, aimed at allowing thorough evaluations.

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FUNDAMENTOS - Ftalocianinas são promissores agentes fotossensibilizadores na terapia fotodinâmica (TFD). OBJETIVOS - Avaliar intervalos, veículos e a incorporação de promotor de absorção na formulação tópica da ftalocianina de zinco (FC-Zn). Avaliar alterações macro e micromorfológicas e a expressão de Fas promovidas pela TFD com FC-Zn tópica no modelo murino. MÉTODOS - Por meio da espectrometria de fluorescência, foram avaliadas combinações de diferentes períodos de oclusão tópica das formulações gel ou emulsão de FC-Zn (1mg/dl), com ou sem monoleína 5 por cento, no dorso do camundongo hairless. Após oito horas das diferentes formulações, os camundongos foram expostos ao laser de diodo de 670nm, dose de 50J/cm-². RESULTADOS - A fluorescência foi discretamente superior após oito horas e com a emulsão nos intervalos de uma, duas e quatro horas de oclusão. A intensidade do edema e da erosão correspondeu à necrose da epiderme e à imunoexpressão de Fas nos cortes histológicos de pele. CONCLUSÕES - Os achados indicam a ação fotodinâmica promovida pela interação entre FC-Zn e fonte de luz de 670nm. As alterações macro e micromorfológicas foram correspondentes e mais substanciais com a emulsão FC-Zn e monoleína, sugerindo a acentuação dos efeitos com essa formulação. A imunoexpressão de Fas e as alterações histológicas sugeriram a apoptose como mecanismo de morte celular na TFD com FC-Zn tópica.

BACKGROUND - Phthalocyanines are promising photosensitizers used in photodynamic therapy (PDT). OBJECTIVES - To evaluate the following parameters: intervals, vehicles and enhancer using topical zinc-phthalocyanine (Zn-PC) formulation. To examine macro and micromorphological changes and Fas expression induced by topical Zn-PC-PDT on murine skin. MATERIAL AND METHODS - Using fluorescence spectrometry, different intervals of topical occlusion employing Zn-PC gel or emulsion, with or without monolein 5 percent were studied. After an 8-hour occlusion of different formulations, the mice were exposed to 670 nm laser, at a 50 J.cm-² dose. RESULTS - Fluorescence was slightly higher after 8 hours, and also with emulsion formulation at one-, two- and four-hour occlusion periods. The intensity of edema and erosion were correlated to epidermal necrosis and to Fas immunoexpression in skin histological specimens. CONCLUSIONS - The results show the effects of photodynamic action promoted by the interaction between Zn-PC formulation and a 670-nm light source. Macro and micromorphological alterations were correlated and more substantial with monolein and Zn-PC emulsion, suggesting more marked effects with this formulation. The Fas immunoexpression and histological changes suggested that apoptosis plays a role in the mechanism of cell death caused by PDT based in Zn-PC.

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Se presenta una panorámica sobre la diversidad de agentes potenciadores de la permeación que son utilizados en la actualidad, así como los procedimientos más frecuentemente empleados para conocer el mecanismo de acción de estas sustancias; además de realizar un recorrido por aspectos teóricos concernientes a la fisiología de la piel y la absorción percutánea. También se hace referencia a los posibles modos de acción en que estos potenciadores actúan y para concluir se mencionan algunas de las técnicas más novedosas para el mejoramiento de la difusión de sustancias activas a través de la barrera cutánea.

It is presented a panorama on the diversity of those agents that enhance permeation and are used at present, as well as on the procedures most frequently used to know the mechanism of action of these substances. The theoretical aspects concerning the skin physiology and the percutaneous absorption are also approached. Reference is made to the possible modes of action in which these enhancers act. To conclude, some of the newest techniques used to improve the diffusion of active substances through the skin barrier are mentioned.