Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available consumer care products that are utilized to prevent vector-borne diseases and skin aging and damage. Semisolid emulsion-based formulation has been extensively selected for active repellent and sunscreen ingredients due to their excellent solubilizing properties for both lipophilic and hydrophilic components and satisfactory customer acceptance. Under the ideal use situation, an appropriate and elegant emulsion-based formulation can minimize transdermal absorption of DEET and oxybenzone and maximize their skin protection effect. The percutaneous penetration profiles of DEET and oxybenzone from several emulsion-based formulations were evaluated and compared by using the in vitro diffusion experiments in this thesis. Various parameters in the emulsion formulations, such as emulsion type, emulsifier, emollient, penetration enhancer, thickening agent, and thixotropic properties of the emulsions, could exert significant influence on percutaneous permeation of the active ingredients from the preparations. An emulsion-based preparation using the emulsifier, Emulium 22, possessed the relatively lower skin permeation of DEET and oxybenzone than other emulsion-based preparations; it was selected for the in vivo animal study. This emulsion-based formulation containing DEET and/or oxybenzone was topically applied to rats once daily for a 60-day period to investigate systemic concentration and tissue deposition of DEET, oxybenzone, and their respective metabolites. This formulation produced lower systemic absorption of DEET and oxybenzone than the commercially available products reported in a previous animal study. The concurrent application of DEET and oxybenzone in this study did not show synergistic enhancement between the two compounds in plasma. The percutaneous penetration profiles of DEET and oxybenzone from different semisolid emulsions in the in vitro diffusion experiment provided the important information in selecting the appropriate formulation of DEET and oxybenzone for topical application. The in vivo animal study identified pharmacokinetics and biodistribution characteristics of DEET and oxybenzone from the promising lab-developed emulsion. Studies are ongoing to further improve formulation characteristics so that this emulsion-based preparation could be used to minimize overall transdermal permeation of DEET and oxybenzone from topical skin application.

Biocandle es un modelo de negocio que busca alcanzar la demanda del mercado de repelentes de insectos. Está diseñado en la presentación de una vela aromática que ahuyenta a los insectos y al mismo tiempo proporciona propiedades de aromaterapia que agregan valor a través de las diferentes esencias utilizadas para su elaboración, y a diferencia de otros productos, está hecho con componentes naturales que no son dañinos. a la salud de las personas. El problema que encontramos y, por lo tanto, nos motivó a llevar a cabo este proyecto es que muchas personas tienen problemas con los insectos, sin embargo, no encuentran la manera perfecta de lidiar con ellos, ya que las alternativas que existen actualmente en el mercado no son agradables. para ellos debido al olor y la toxicidad en el caso de tabletas repelentes o repelentes en aerosol y la textura cuando se aplica a la piel en el caso de repelentes en crema. Para comprender el problema, hicimos un análisis del mercado a través de entrevistas y, en consecuencia, pudimos validar el interés en el producto descrito anteriormente. Además, aplicamos diferentes herramientas durante el proyecto, tales como DAFO, marketing y recursos humanos, finanzas y análisis de costos con datos reales de los suministros necesarios para la elaboración y el costo de entrega, entre otros. / Biocandle is a business model that seeks to reach the market demand of insect repellents. It is designed in the presentation of an aromatic candle that drives away insects and at the same time it provides aromatherapy properties which add value through the different essences used for its elaboration, and unlike other products, it is made with natural components that are not harmful to people's health. The problem we have found and therefore, motivated us to carry out this project is that many people have problems with insects, however, they do not find the perfect way to deal with them, since the alternatives that currently exist in the market are not pleasant for them due to the smell and toxicity in the case of repellent tablets or spray repellents and the texture when applied to the skin in the case of cream repellents. To understand the problem, we did an analysis to the market through interviews and in consequence, we were able to validate the interest in the product described above. Moreover, we applied different tools during the project such as SWOT, marketing and human resources, Finance and cost analysis with real data of the supplies needed for the elaboration and delivery cost, among others. / Trabajo de investigación

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

El objetivo de esta Tesis Doctoral es estudiar diferentes herramientas para el manejo de plagas y enfermedades del cultivo de la platanera. Entre las herramientas que vamos a desarrollar, se van a analizar los compuestos orgánicos volátiles (COVs) fúngicos derivados de hongos entomopatógenos (HE) y nematófagos, como fuente de metabolitos con actividad antagónica contra el picudo negro (PN) de la platanera, Cosmopolites sordidus, para su control y manejo en el campo. Así mismo, vamos a estudiar las respuestas de cultivares de plataneras a quitosano, un polisacárido biodegradable, para evaluar su posible uso en el campo como estimulante y protector de las plantas frente a plagas y patógenos, como Fusarium oxysporum f. sp. cubense. El conjunto de capítulos de esta tesis pretende sentar las bases de una estrategia de manejo sostenible de plagas y enfermedades del cultivo de la platanera, basada en el uso de COVs derivados de hongos presentes de forma natural en los cultivos, en combinación con la suplementación de quitosano en el riego, para un efecto de protección y activación de las defensas de las plataneras antes de cualquier infección de plagas y/o enfermedades. El objetivo principal de esta Tesis Doctoral es encontrar nuevas fórmulas para la gestión integrada de plagas como Cosmopolites sordidus y enfermedades de la platanera en condiciones de campo. En esta Tesis Doctoral hemos ideado enfoques sostenibles para la gestión de las plagas y enfermedades de las plataneras. Nuestros objetivos son: a) Cosmopolites sordidus (picudo negro de la platanera, PN), la principal plaga de los cultivos de plátano y, b) el hongo del marchitamiento Fusarium oxysporum f. sp. cubense Raza Tropical 4 (FocTR4), agente causante de una nueva variante extremadamente virulenta de la enfermedad del “Mal de Panamá”, que se está extendiendo rápidamente por todo el mundo. Nuestras herramientas de gestión sostenible son: a) los hongos entomopatógenos (HE, conocidos por su uso como agentes de control biológico, ACBs) aislados de campos comerciales de plátanos, b) sus compuestos orgánicos volátiles (COVs) y, c) el quitosano, un compuesto biodegradable y elicitor de la inmunidad de las plantas con actividad antimicrobiana. Damos evidencia de que los COVs de los hongos agentes de control biológico son repelentes del PN. Pueden utilizarse en los cultivos de platanera mediante estrategias de push and pull para gestionar la plaga de forma sostenible. El quitosano puede utilizarse en el riego para prevenir las defensas de la platanera local y sistémicamente. Por lo tanto, este polímero, con probada actividad antimicrobiana frente a otros patógenos de marchitamiento de Fusarium spp., podría utilizarse contra la actual pandemia en las plataneras causada por FocTR4. La capacidad de inducir reguladores del crecimiento de las plantas sostiene también el papel fertilizante del quitosano. La inducción de compuestos relacionados con la respuesta sistémica adquirida (RSA) hace que el riego con quitosano sea una herramienta para manejar también las plagas de las plataneras sobre el suelo (PN) y las enfermedades (Sigatoka). De esta manera, los COVs y el quitosano podrían ayudar a reducir el uso de agroquímicos tóxicos en los cultivos de platanera en todo el mundo.