Transdermal Delivery Systems Based on Natural Polymeric Biomaterials

The human skin provides a unique delivery pathway for therapeutic and other active agents. Although several approaches have been proposed and implemented, including the use of syn-thetic and natural polymers, there is a persistent pursuit of alternative biomaterials for enhanc-ing the development of transdermal delivery systems. Therefore, in this study, natural poly-mers, namely the chitin-glucan complex (CGC), FucoPol, and polyhydroxyalkanoates (PHA), have been prospected for use as biomaterials for the fabrication of hydrogels and micronee-dles (MN) arrays, two innovative approaches for efficient and controlled drug delivery through the skin. CGC was solubilized using NaOH/urea solvent systems through a freeze/thaw procedure, overcoming its previous insolubility challenge. This approach resulted in a significant solubili-zation rate of 63–68%, yielding a chitosan-glucan complex (ChGC). Based on this process, hy-drogels were fabricated using different alkali solvent systems, NaOH and KOH solutions, via a freeze-thaw procedure. The hydrogels exhibited varying microstructures, viscoelastic proper-ties, and textures depending on the type of solvent used and their ionic strength. Furthermore, the hydrogels were biocompatible. Subsequently, optimization of the process parameters al-lowed the reduction of the time needed to prepare the CGC hydrogels, and the optimized structures demonstrated a spontaneous swelling ratio and good water retention capacity. When loaded with caffeine, hydrogels' mechanical and rheological properties were significantly affected, and the caffeine release rate depended on the pH and ionic strength of the surround-ing solution. Additionally, it was shown that increasing the CGC concentration led to the for-mation of hydrogels with a denser and tighter microstructure and increased their mechanical and rheological parameters. The hydrogels were loaded with different types of active pharma-ceutical ingredients (APIs), exhibiting permeation fluxes through artificial membranes corre-lated to the APIs' physicochemical characteristics. FucoPol was used as a structuring agent to fabricate hydrogel membranes (HMs) using Fe3+ as a crosslinker. It was demonstrated that, after a threshold of 1.5 g/L, Fe3+ concentration had a limited effect on HMs strength, while varying the concentration of FucoPol significantly in-fluenced their properties. Three FucoPol concentrations (1.0, 1.75, and 2.5wt%) combined with Fe3+ (1.5 g/L) resulted in HMs with varying microstructures, swelling ratios, and hardness values. These HMs were non-cytotoxic and exhibited anti-inflammatory properties. Additionally, the FucoPol HMs were loaded with caffeine or diclofenac sodium using different methods to assess drug loading capacity. The results showed that the loading method had an impact on the me-chanical and rheological properties of the HMs and led to distinct drug release profiles. PHAs with different compositions, including homopolymer poly(3-hydroxybutyrate) (PHB), copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) with varying HV content (14, 43, and 87wt%), and terpolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hy-droxyhexanoate) (PHBVHx), were used to fabricate MNs through a micromolding process. While these biopolymers were successfully utilized for MN fabrication, their distinct physico-chemical properties led to MNs with differing characteristics. PHB, PHBV (43% HV), and PHBVHx produced sharp MNs with similar failure forces (~5.5 N), suggesting the ability to pierce the human skin. PHBVHx MNs displayed greater deformation resistance and insertion studies in Parafilm multilayer systems revealed their ability to penetrate up to 396 μm without breaking. Furthermore, diclofenac sodium was coated onto PHBVHx MNs and the resulting coated MNs exhibited comparable failure forces, decreased mechanical stiffness, and a rapid drug release profile. Overall, this work demonstrated that the natural polymers CGC, FucoPol, and PHAs can be used as structuring agents for the development of novel biomaterials, namely, hydrogels and MNs, with very promising properties, thus contributing to the sustainable fabrication of im-proved transdermal delivery systems.A pele humana proporciona uma via de administração única para agentes terapêuticos e outros compostos ativos. Embora várias abordagens tenham sido propostas e implementadas, incluindo o uso de polímeros sintéticos e naturais, persiste a procura por biomateriais alterna-tivos para melhorar o desenvolvimento de sistemas de administração transdérmica. Assim, nesta tese foram utilizados biomateriais naturais, nomeadamente o complexo quitina-glucano (CQG), FucoPol e polihidroxialcanoatos (PHAs), na fabricação de hidrogéis e matrizes de mi-croagulhas (MN), duas abordagens inovadoras para entrega eficiente e controlada de fármacos através da pele. CQG foi solubilizado utilizando sistemas de solventes NaOH/ureia através de um procedi-mento de congelamento/descongelamento, superando seu desafio de insolubilidade. Esta abordagem resultou em uma taxa de solubilização significativa de 63–68%, produzindo um complexo quitosano-glucano (ChGC). Com base nesse processo, foram fabricados hidrogéis utilizando diferentes sistemas de solventes alcalinos, nomeadamente soluções de NaOH e KOH, por meio de um procedimento de congelamento/descongelamento. Esses hidrogéis apresentaram microestruturas, propriedades viscoelásticas e texturas variáveis, dependendo do tipo de solvente utilizado e da sua força iónica. Além disso, os hidrogéis demonstraram ser biocompatíveis. Posteriormente, a otimização dos parâmetros do processo permitiu a redução do tempo necessário para preparar os hidrogéis, e as estruturas otimizadas demonstraram absorção de água espontânea, bem como uma boa capacidade de retenção de água. Quando carregados com cafeína, as propriedades mecânicas e reológicas dos hidrogéis foram signifi-cativamente afetadas, e a taxa de liberação de cafeína dependeu do pH e da força iónica da solução de libertação. Além disso, foi demonstrado que o aumento da concentração de CQG levou à formação de hidrogéis com uma microestrutura mais densa e compacta, e ao aumento dos parâmetros mecânicos e reológicos. Os hidrogéis de CQG foram capazes de ser carregados com diferentes tipos de ingredientes farmacêuticos ativos (APIs), exibindo fluxos de permeação através de membranas artificiais correlacionados com as características físico-químicas dos APIs. FucoPol foi utilizado como agente estruturante no fabrico de membranas de hidrogel (HMs) usando Fe3+ como reticulante. Foi demonstrado que, acima de um valor de 1,5 g/L, a concen-tração de Fe3+ tem um efeito limitado na resistência das membranas, enquanto a variação da concentração de FucoPol influenciou significativamente suas propriedades. Três concentrações de FucoPol (1,0, 1,75 e 2,5%) combinadas com Fe3+ (1,5 g/L) resultaram em membranas com diferentes microestruturas, capacidade de absorção de água e propriedades mecânicas. As membranas demonstraram ser biocompatíveis, exibindo propriedades anti-inflamatórias. Além disso, as membranas de FucoPol foram carregadas com cafeína ou diclofenac de sódio através de diferentes métodos para avaliar a sua capacidade de incorporação de fármacos. Os resul-tados demostraram que o método de incorporação utilizado teve impacto nas propriedades mecânicas e reológicas das membranas, levando a perfis distintos de libertação. PHAs com diferentes composições, incluindo PHB, PHBV com diferentes conteúdos em 3HV (14, 43 e 87%), e PHBVHx, foram usados para fabricar MNs através de um processo de micro-moldagem por fusão. Embora estes biopolímeros tenham sido bem-sucedidos no fabrico das MNs, as suas distintas propriedades físico-químicas resultaram em MNs com características diferentes. PHB, PHBV contendo 43% em 3HV, e PHBVHx produziram MNs pontiagudas com forças de falha semelhantes (~5,5 N), sugerindo capacidade de perfurar a pele humana. As MNs de PHBVHx exibiram maior resistência à deformação e estudos de inserção em sistemas multicamadas de Parafilm revelaram a sua capacidade de penetrar até 396 μm sem quebrar. Além disso, diclofenac de sódio foi utilizado para revestir MNs de PHBVHx, sendo que as MNs revestidas apresentaram forças de falha comparáveis às MNs não revestidas, rigidez mecânica diminuída e um perfil de libertação rápida do fármaco. No geral, esta tese demonstrou que os polímeros naturais CGC, FucoPol e PHAs podem ser usados como agentes de estruturação para o desenvolvimento de novos biomateriais, nome-adamente, hidrogéis e MNs, com propriedades muito promissoras, contribuindo, assim, para a fabricação sustentável de melhores sistemas de administração transdérmica

Production of chitin-glucan complex by Pichia pastoris

Dissertation for the Degree of Master in BiotechnologyThe yeast Pichia pastoris produces chitin-glucan complex (CGC), as a cell wall component. CGC is composed of two types of biopolymers, chitin and β-glucans, which confer it great potential for use in the food, cosmetic and pharmaceutical industries. CGC hydrolysis, allows obtaining chitin/chitosan and glucans individually. The chitin and chitosan obtained from CGC have the considerable advantage of being of non-animal origin, which further extends their applications. In last year’s, the production of CGC by Pichia pastoris was realized with glycerol as sole carbon source, achieving high cell density. In this study, different substrates were tested for cultivation of P. pastoris and CGC production. In the first part, mixtures of glucose and xylose, in varying proportions, were tested. Since glucose and xylose are two of the main sugar components of lignocellulosic wastes, the ability of P. pastoris to use them as carbon sources would allow their valorization into value-added products. In the second part, several wastes and byproducts generated by different industries were tested for their suitability as substrates for P. pastoris cultivation. In study of the glucose/xylose mixtures, the best performance was achieved in batch bioreactor experiments with 25% xylose in the medium (20 gL-1 of xylose and 60 gL-1 of glucose), where 35.25 gL-1 biomass was obtained in 64 hours of cultivation. CGC content in the cell wall reached 15% with a volumetric productivity of 0.085 gL-1.h-1. The molar ratio of chitin:β-glucan in the extracted biopolymer was 47:53, higher than obtained with crude glycerol (16:84). In the second part of study, several wastes and byproducts (used cooking oil, sugarcane molasses, cheese whey, waste paper and spent coffee grounds) were tested. The results show that P. pastoris presented low biomass concentration using any of these substrates. Nevertheless, in batch bioreactor experiments the best results were achieved with sugarcane molasses, where 17.78 gL-1 biomass were obtained with a CGC content of 17%. Among the tested substrates, the mixtures of glucose/xylose appear to be the most promising due the good CGC production obtained and the high glucosamine molar fraction in produced polymer. This study opens the hypothesis of utilization of lignocellulosic materials with xylose percentages up to 50%

Biovalorization of lignocellulosic materials for xylitol production by the yeast komagataella pastoris

The main goal of this study was to screen different lignocellulosic materials for their ability to support the cell growth of the yeast Komagataella pastoris and the production of xylitol. Several lignocellulosic materials, namely banana peels, brewer’s spent grains (BSGs), corncobs, grape pomace, grape stalks, and sawdust, were subjected to dilute acid hydrolysis to obtain sugar rich solutions that were tested as feedstocks for the cultivation of K. pastoris. Although the culture was able to grow in all the tested hydrolysates, a higher biomass concentration was obtained for banana peels (15.18 ± 0.33 g/L) and grape stalks (14.58 ± 0.19 g/L), while the highest xylitol production (1.51 ± 0.07 g/L) was reached for the BSG hydrolysate with a xylitol yield of 0.66 ± 0.39 g/g. Cell growth and xylitol production from BSG were improved by detoxifying the hydrolysate using activated charcoal, resulting in a fourfold increase of the biomass production, while xylitol production was improved to 3.97 ± 0.10 g/L. Moreover, concomitant with arabinose consumption, arabitol synthesis was noticed, reaching a maximum concentration of 0.82 ± 0.05 g/L with a yield on arabinose of 0.60 ± 0.11 g/g. These results demonstrate the feasibility of using lignocellulosic waste, especially BSG, as feedstock for the cultivation of K. pastoris and the coproduction of xylitol and arabitol. Additionally, it demonstrates the use of K. pastoris as a suitable microorganism to integrate a zero-waste biorefinery, transforming lignocellulosic waste into two high-value specialty chemicals with high market demand.publishersversionpublishe

Margem muro

Anais do V Encontro de Iniciação Científica e I Encontro Anual de Iniciação ao Desenvolvimento Tecnológico e Inovação – EICTI 2016 - 05 e 07 de outubro de 2016 – Sessão Linguística, Letras e ArtesDurante a sabida trajetória do coletivo de nossa espécie pela extensão da esfera terrestre, poucas manifestações de nossa característica industria se mostraram tão resilientes (e em tamanha cumplicidade) quanto o objeto “muro”, tão pluralmente encarnado, ante as distintas carências humanas — desde seu advento. Suas propriedades plásticas — para além de suas funções basilares — constituem caracteres emblemáticos que sobremaneira transcendem sua palpável existência em significações outras, igualmente relevantes. Pensá-lo enquanto constante — em relação ao sabido desvelar da experiência humana — nos empodera a investigar sua intrínseca relação com os campos da expressão e da arte, tanto nos primórdios de nossa experiência quanto no presente estado de nossa marcha. O projeto presente, portanto, se caracteriza pela investigação aprofundada do fenômeno que, em um momento anterior (nos 6 meses que antecederam a feitura da presente empresa), verificamos em pesquisa de campo: a ocupação do muro por meios artístico-expressivos na região das três fronteiras (Brasil, Argentina e Paraguai). Partindo, por conseguinte, dos questionamentos originados desta primeira experiência, propomos assim uma análise deste objeto com o fito de melhor situar os processos com os quais nos deparamos em campo, nos entornos da fronteira

Defining and measuring learning outcomes in Portuguese Higher Education

Os resultados de aprendizagem assumem-se como importante ferramenta no quadro do Ensino Superior, já que permitem descrever os conhecimentos e competências que se espera que os estudantes demonstrem no final da sua formação. Este estudo descreve o nível de implementação, dos resultados de aprendizagem no contexto nacional, explorando quais as competências mais valorizadas nos perfis de saída dos seus diplomados (1º, 2º e 3º ciclos). Partindo de uma metodologia mista, foi elaborada uma matriz de análise, validada teórica e empiricamente. Esta taxonomia integra competências específicas à área científica e um conjunto alargado de competências transversais, possibilitando uma leitura compreensiva dos resultados de aprendizagem.The learning outcomes become an important tool in the Higher Education system, since they allow to describe the knowledge and skills that students are expected to acquire at the end of their training. This study intends to evaluate the level of implementation of learning outcomes in the national context, exploring which competences are most valued in the professional profiles of their graduates. Based on a mixed methodology, a matrix of analysis was elaborated, and was validated both theoretical and empirically. This taxonomy integrates discipline-specific competences and a wide range of transversal competences, allowing a comprehensive reading of RA.info:eu-repo/semantics/publishedVersio

Protective multifunctional fibrous systems based on natural fibers and metal oxide nanoparticles

In recent years, an unprecedented increase in the development of products and technologies to protect the human being has been observed. Now, more than ever, the world population is exposed to several threats, harmful to their well-being and health. Chemical and biological hazardous agents stand out as one of the biggest threats, not only for the military forces, but also for the civilians. Consequently, it’s essential to develop personal protective systems that are able to protect their user, not only passively, but actively, being able to detect, adsorb, degrade and decontaminate pesticides, pollutants, microorganisms and most importantly: chemical/biological warfare agents. One recent strategy for the development of active fibrous structures with improved functions and new properties is their functionalization with nanoparticles (NPs), especially metal oxides. Although their known effectiveness in the decomposition of harmful agents, the NPs could also include other functionalities in the same structure using low quantities of material, without adding extra weight, which is of huge importance for a soldier in the battlefield. The use of natural fibers as the substrate is also very interesting, since this material is a much sustainable alternative when compared to synthetic ones, also providing excellent properties.The authors are thankful to project UID/CTM/00264/2021 of 2C2T—Centro de Ciência e Tecnologia Têxtil, funded by National Founds through FCT/MCTES—Fundação para a Ciência e a Tecnologia D.P.F. is thankful to CEECIND/02803/2017 and J.C.A. to the FCT PhD Scholarship (SFRH/BD/147812/2019), founded by National Founds through FCT/MCTES

Chitin-Glucan Complex Hydrogels: Optimization of Gel Formation and Demonstration of Drug Loading and Release Ability

Chitin-glucan complex (CGC) hydrogels were fabricated through a freeze–thaw procedure for biopolymer dissolution in NaOH 5 mol/L, followed by a dialysis step to promote gelation. Compared to a previously reported methodology that included four freeze–thaw cycles, reducing the number of cycles to one had no significant impact on the hydrogels’ formation, as well as reducing the total freezing time from 48 to 18 h. The optimized CGC hydrogels exhibited a high and nearly spontaneous swelling ratio (2528 +- 68%) and a water retention capacity of 55 +- 3%, after 2 h incubation in water, at 37 ºC. Upon loading with caffeine as a model drug, an enhancement of the mechanical and rheological properties of the hydrogels was achieved. In particular, the compressive modulus was improved from 23.0 +-0.89 to 120.0 +- 61.64 kPa and the storage modulus increased from 149.9 +- 9.8 to 315.0 +- 76.7 kPa. Although the release profile of caffeine was similar in PBS and NaCl 0.9% solutions, the release rate was influenced by the solutions’ pH and ionic strength, being faster in the NaCl solution. These results highlight the potential of CGC based hydrogels as promising structures to be used as drug delivery devices in biomedical applicationsinfo:eu-repo/semantics/publishedVersio

Acciones performáticas y prácticas sociales en la Triple Frontera

Anais do II Encontro de Iniciação Científica e de Extensão da Unila - Sessão de Música, Linguística e Literatura - 03/07/13 – 13h30 às 18h30 - Unila-PTI - Bloco 09 – Espaço 03 – Sala 03En un territorio geogr ́a fico como la Triple Frontera (¿o en un territorio art ́ ıstico como la performance?) el imaginario colectivo se articula en m ́ ultiples espacios dispuestos para el inter- cambio y convergencia, como tambi ́en para conflictos de distintos ́ ordenes. La triple frontera - continuamente construida - se debate entre diferentes discursos enraizados en distintas esfe- ras: desde discursos externos con repercusi ́ on interna (regi ́ on sin ley, v ́ertice del narcotr ́ a fico) hasta voces internas que quieren ser escuchadas (la segunda regi ́on de mayor intercambio co- mercial, una de las 7 maravillas de la naturaleza). Contempor ́ aneamente a este problem ́ atico concepto hacemos referencia a un t ́ermino tambi ́en en si mismo lim ́ ıtrofe, fronterizo, en el ́ area de la po ́etica: la performance, lenguaje art ́ ıstico en contra de la jerarqu ́ ıa impuesta por medio de factores externos (el mercado, el poder instituido) en el cual se dinamizan varios elementos o ́ ambitos art ́ ısticos preexistentes (teatro, danza, pintura, m ́ usica, etc.). Para este an ́alisis es necesario establecer un puente de mediaci ́on entre las dos tem ́aticas, un abordaje desde el cual podamos intervenir en la conversaci ́on de los conflictos geogr ́a fico-art ́ ısticos, un pasillo en el cual podamos caminar e interactuar con la idea y la pr ́actica de la frontera, entendida como un espacio de relaciones convergentes a la vez que de conflictos. En este sentido, trabajaremos con las siguientes obras perform ́aticas construidas en este lugar (Milton Santos): La custodia - a-1 53167, Opera ̧c ̃ao nas Cataratas - Paulo Bruscky e Ipor ̃a Lenda Show. ¿Cuales son las din ́amicas seguidas por un concepto en disputa como la Triple Frontera y por un conflicto de frontera paralelo, la performance?, y finalmente ¿Cuales son los ejercicios que distribuyen y legitiman las im ́agenes hacia un imaginario colectivo propio de una regi ́on como lo es la Triple Frontera, en permanente ”guerra cultural”(Teixeira Coelho)?Universidade Federal da Integração Latino-Americana (UNILA