Analgesia posoperatoria en la videolaparascopía de urgencia mediante irrigación de bupivacaína intraperitoneal / Posoperative analgesia in emergency videolaparoscopy through intraperitoneal bupivacaine irrigation

Introducción: La videolaparascopía es un procedimiento frecuente en los servicios de urgencias de cirugía general. El dolor agudo después de estas intervenciones es de naturaleza compleja y requiere un tratamiento analgésico efectivo. Objetivo: Determinar la utilidad del empleo de bupivacaína intraperitoneal en el alivio del dolor posoperatorio en la videolaparascopía de urgencia. Métodos: Se realizó un estudio longitudinal prospectivo y analítico en 80 pacientes mayores de 18 años, anunciados para videolaparoscopía bajo anestesia general orotraqueal en el servicio de urgencias del HMC: Dr. Luis Díaz Soto, desde septiembre de 2016 hasta septiembre de 2018. Los pacientes fueron divididos aleatoriamente en dos grupos de 40 cada uno. Al grupo 1 se aplicó lidocaína transdérmica preincisional en las incisiones de piel y, al término de la cirugía, se irrigaron ambos hemidiafragmas con bupivacaína al 0,25 por ciento. Al grupo 2 se le administró dosis preincisional de analgésicos endovenosos solamente. Resultados: Predominó significativamente el sexo femenino sin diferencia entre grupos. La analgesia posoperatoria fue mejor en el grupo 1 estadísticamente significativa a las 4, 8 y 12 horas. Los requerimientos de analgesia de rescate fueron menores en el grupo 1 (p=0,0024). No se reportaron efectos adversos. Conclusiones: La administración de lidocaína transdérmica preincisional y la instilación de bupivacaína intraperitoneal al final de la videolaparoscopía de urgencia, reduce significativamente el dolor en las primeras horas de posoperatorio. Su aplicación es sencilla, fácil y segura sin evidencias de efectos adversos(AU)

Introduction: Videolaparoscopy is a frequent general surgery procedure in emergency services. Acute pain after these interventions is complex in nature and requires effective analgesic treatment. Objective: To determine the usefulness of intraperitoneal bupivacaine in the relief of postoperative pain in emergency videolaparoscopy. Methods: A prospective, analytical and longitudinal study was carried out in eighty patients older than eighteen years old, announced for videolaparoscopy under orotracheal general anesthesia in the emergency department of Hospital Militar Central Dr. Luis Díaz Soto, from September 2016 to September 2018. The patients were randomly divided into two groups of forty individuals each. Group 1 was applied pre-incisional transdermal lidocaine on skin incisions and, at the end of surgery, both hemidiaphragms were irrigated with bupivacaine 0.25 percent. Group 2 received pre-incisional doses of intravenous analgesics only. Results: The female sex predominated significantly, without difference between the two groups. Postoperative analgesia was better in group 1, insofar it was statistically significant at four, eight and twelve hours. Rescue analgesia requirements were lower in group 1 (p=0.0024). No adverse effects were reported. Conclusions: The administration of pre-incisional transdermal lidocaine and the instillation of intraperitoneal bupivacaine at the end of emergency videolaparoscopy significantly reduces pain during the first hours after surgery. Its application is simple, easy and safe, without evidence of adverse effects(AU)

Transferosomas conteniendo ftalocianina de aluminio clorada como alternativa terapéutica en leishmaniasis cutánea: permeabilidad y biodistribución en ratas Wistar / Transferosomes loaded with chloroaluminum phthalocyanine as cutaneous leishmaniasis therapeutic alternative: permeability and biodistribution in Wistar rats

Resumen Objetivo: Evaluar la permeabilidad, retención y biodistribución de los LUD-PcAlCl in vivo. Metodología: Los transferosomas fueron obtenidos mediante rehidratación de película lipídica. Ratas Wistar fueron tratadas tópica e intraperitonealmente con los transferosomas por 5 días. La penetración ex vivo fue determinada mediante el ensayo en celdas de Franz y la retención por el método de la cinta adhesiva. Cinco y treinta días postratamiento se obtuvo la piel y órganos para determinar la retención del compuesto y realizar estudios histopatológicos. La PcAlCl fue extraída con solventes y cuantificada por fluorometría. Los resultados se expresaron en nM PcAlCl/mg órgano. Resultados: La PcAlCl no penetró la piel en los ensayos ex vivo, reteniéndose principalmente en el estrato córneo. Cinco días post-tratamiento tópico la PcAlCl fue retenida en estrato córneo (41,76±0,02), mostrando concentraciones mínimas en bazo (0,09±0,02), epidermis-dermis (0,06±0,17), hígado (0,03±0,02) y pulmón (0,02±0,01 nM). Por vía intraperitoneal se encontró PcAlCl en bazo (0,58±0,4), cerebro (0,07±0,07), corazón (0,07±0,12), pulmón (0,012±0,01) y piel (0,021±0,02 nM). Treinta días postratamiento no se encontró PcAlCl en ningún órgano. Los estudios histopatológicos fueron negativos. Conclusión: La PcAlCl contenida en transferosomas fue retenida principalmente en estrato córneo, mostrando bajas concentraciones en la dermis, sitio donde se aloja el parásito. Se sugiere modificar los componentes vesiculares del sistema para aumentar la permeación del compuesto.

Abstract Objective: To assess the UDL-ClAlPc permeability, retention and biodistribution in vivo. Methods: Transferosomas were obtained by lipid film re-hydration method. Wistar rats were treated topically and intraperitoneally with UDL-ClAlPc for 5 days. Skin and organs were collected five and thirty days after-treatment to determine ClAlPc retention and histopatho-logical studies. The ClAlPc was extracted with solvents and quantified by fluorometry. The results were expressed in nM PcAlCl/mg organ. The permeation was tested ex vivo using Franz-diffusion cells and the retention in stratum corneum and epidermis-dermis by tape stripping. Results: In the ex vivo experiments ClAlPc-UDL was not able to penetrate rat skin and was retained mainly in the stratum corneum. In rat, five days after topical treatment ClAlPc was retained mainly in the stratum corneum (41.76±0.02) with minimum concentrations in spleen (0.09±0.02), epidermis-dermis (0.06±0.17), liver (0.03±0.02) and lung (0.02±0.01 nM). After intra peritoneal treatment, ClAlPc was found in spleen (0.58±0.4), brain (0.07±0.07), heart (0.07±0.12), lung (0.01±0.012) and skin (0.021±0.02 nM). Thirty days post-treatment ClAlPc was not found in any organ. Histopathological studies were negative. Conclusion: The ClAlPc contained in transferosomes was retained mainly in the stratum corneum. Low concentration was detected in dermis a place where the parasite survives. This vehicle needs to be improved to increase skin penetration.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC). The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

O objetivo deste trabalho foi o desenvolvimento e a validação de metodologia empregando a célula de difusão vertical para avaliação da liberação e permeação cutânea in vitro de nicotina a partir de adesivos transdérmicos. A célula de difusão vertical é considerada um aparato experimental importante em pesquisa e desenvolvimento e pode simular condições in vitro próximas aquelas observadas em ensaios clínicos. Neste trabalho foram avaliados dois dispositivos transdérmicos comercializados no Brasil para liberação controlada de 14 mg de nicotina em um período de 24 horas. Realizaram-se ensaios de liberação, usando membranas de diálise de celulose regenerada, e estudos de permeação cutânea, usando pele de orelha de porcos. Os resultados indicaram que a liberação da nicotina em ambos os dispositivos transdérmicos avaliados seguiu a cinética de Higuchi, enquanto que a permeação cutânea seguiu cinética de ordem zero. As velocidades de liberação foram diferentes para os dispositivos comerciais avaliados, entretanto não foram encontradas diferenças significativas para as velocidades de permeação cutânea. Conforme os estudos de validação, a metodologia mostrou-se apropriada para a avaliação in vitro da liberação e permeação cutânea a partir de adesivos transdérmicos de nicotina. O método proposto foi aplicado em estudos comparativos in vitro entre adesivos transdérmicos comerciais contendo nicotina. Deste modo, o método também pôde ser considerado como ferramenta útil que poderia ser aplicada durante o desenvolvimento de novas formulações transdérmicas para liberação de nicotina.

Administração cutânea de fármacos: desafios e estratégias para o desenvolvimento de formulações transdérmicas / Cutaneous administration of drugs: challenges and strategies for the development of transdermal formulations

O desenvolvimento de formulações para aplicação na pele é uma estratégia interessante para transportar fármacos cuja ação é a própria pele, representando uma alternativa para superar aspectos indesejados relacionados às características farmacocinéticas e farmacodinâmicas dos fármacos. No entanto, a pele apresenta camadas que formam uma barreira à penetração de fármacos. Desse modo, estratégias têm sido pesquisadas e os modernos estudos farmacêuticos apontam para o uso de métodos físicos e químicos, norteados no desenvolvimento de novas formas farmacêuticas, as quais devem apresentar propriedades físico-químicas e parâmetros farmacotécnicos adequados para o uso transdérmico.

The development of formulations for skin application is a good strategy for the delivery of drugs whose target is the skin itself, which avoids some unwanted effects of treatment arising from the pharmacokinetic and pharmacodynamic properties of drugs. However, the skin has layers that resist the penetration of drugs. Thus, new strategies have been researched and the latest pharmaceutical studies point to the use of physical and chemical methods aimed at the development of new drug delivery systems, exhibiting physicochemical properties and pharmaceutical parameters suitable for transdermal administration.