A carregar...
Projeto de investigação
Transdermal delivery systems based on natural polymeric biomaterials
Financiador
Autores
Publicações
Chitin-Glucan Complex Hydrogels
Publication . Araújo, Diana; Rodrigues, Thomas; Roma-Rodrigues, Catarina; Alves, Vítor D.; Fernandes, Alexandra R.; Freitas, Filomena; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; DCV - Departamento de Ciências da Vida; MDPI - Multidisciplinary Digital Publishing Institute
Chitin-glucan complex (CGC) hydrogels were fabricated by coagulation of the biopolymer from an aqueous alkaline solution, and their morphology, swelling behavior, mechanical, rheological, and biological properties were studied. In addition, their in vitro drug loading/release ability and permeation through mimic-skin artificial membranes (Strat-M) were assessed. The CGC hydrogels prepared from 4 and 6 wt% CGC suspensions (Na51*4 and Na51*6 hydrogels, respectively) had polymer contents of 2.40 ± 0.15 and 3.09 ± 0.22 wt%, respectively, and displayed a highly porous microstructure, characterized by compressive moduli of 39.36 and 47.30 kPa and storage moduli of 523.20 and 7012.25 Pa, respectively. Both hydrogels had a spontaneous and almost immediate swelling in aqueous media, and a high-water retention capacity (>80%), after 30 min incubation at 37 °C. Nevertheless, the Na51*4 hydrogels had higher fatigue resistance and slightly higher-water retention capacity. These hydrogels were loaded with caffeine, ibuprofen, diclofenac, or salicylic acid, reaching entrapment efficiency values ranging between 13.11 ± 0.49% for caffeine, and 15.15 ± 1.54% for salicylic acid. Similar release profiles in PBS were observed for all tested APIs, comprising an initial fast release followed by a steady slower release. In vitro permeation experiments through Strat-M membranes using Franz diffusion cells showed considerably higher permeation fluxes for caffeine (33.09 µg/cm2/h) and salicylic acid (19.53 µg/cm2/h), compared to ibuprofen sodium and diclofenac sodium (4.26 and 0.44 µg/cm2/h, respectively). Analysis in normal human dermal fibroblasts revealed that CGC hydrogels have no major effects on the viability, migration ability, and morphology of the cells. Given their demonstrated features, CGC hydrogels are very promising structures, displaying tunable physical properties, which support their future development into novel transdermal drug delivery platforms.
Chitin-Glucan Complex Hydrogels: Optimization of Gel Formation and Demonstration of Drug Loading and Release Ability
Publication . Araújo, Diana; Rodrigues, Thomas; Alves, Vítor D.; Freitas, Filomena; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; MDPI - Multidisciplinary Digital Publishing Institute
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◦C. 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 applications.
Biovalorization of lignocellulosic materials for xylitol production by the yeast komagataella pastoris
Publication . Araújo, Diana; Costa, Tatiana; Freitas, Filomena; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; MDPI - Multidisciplinary Digital Publishing Institute
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.
Deacetylation and Desuccinylation of the Fucose-Rich Polysaccharide Fucopol
Publication . Baptista, Sílvia; Araújo, Diana; Concórdio-Reis, Patrícia; Marques, Ana C.; Fortunato, Elvira; Alves, Vítor D.; Freitas, Filomena; DQ - Departamento de Química; UCIBIO - Applied Molecular Biosciences Unit; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; UNINOVA-Instituto de Desenvolvimento de Novas Tecnologias; MDPI - Multidisciplinary Digital Publishing Institute
FucoPol is an acylated polysaccharide with demonstrated valuable functional properties that include a shear thinning fluid behaviour, a film-forming capacity, and an emulsion forming and stabilizing capacity. In this study, the different conditions (concentration, temperature, and time) for alkaline treatment were investigated to deacylate FucoPol. Complete deacetylation and desuccinylation was achieved with 0.02 M NaOH, at 60 °C for 15 min, with no significant impact on the biopolymer’s sugar composition, pyruvate content, and molecular mass distribution. FucoPol depyruvylation by acid hydrolysis was attempted, but it resulted in a very low polymer recovery. The effect of the ionic strength, pH, and temperature on the deacetylated/desuccinylated polysaccharide, d-FucoPol, was evaluated, as well as its emulsion and film-forming capacity. d-FucoPol aqueous solutions maintained the shear thinning behaviour characteristic of FucoPol, but the apparent viscosity decreased significantly. Moreover, contrary to FucoPol, whose solutions were not affected by the media’s ionic strength, the d-FucoPol solutions had a significantly higher apparent viscosity for a higher ionic strength. On the other hand, the d-FucoPol solutions were not affected by the pH in the range of 3.6–11.5, while FucoPol had a decreased viscosity for acidic pH values and for a pH above 10.5. Although d-FucoPol displayed an emulsification activity for olive oil similar to that of FucoPol (98 ± 0%) for an oil-to-water ratio of 2:3, the emulsions were less viscous. The d-FucoPol films were flexible, with a higher Young′s modulus (798 ± 152 MPa), a stress at the break (22.5 ± 2.5 MPa), and an elongation at the break (9.3 ± 0.7%) than FucoPol (458 ± 32 MPa, 15.5 ± 0.3 MPa and 8.1 ± 1.0%, respectively). Given these findings, d-FucoPol arises as a promising novel biopolymer, with distinctive properties that may render it useful for utilization as a suspending or emulsifier agent, and as a barrier in coatings and packaging films.
Novel Hydrogel Membranes Based on the Bacterial Polysaccharide FucoPol
Publication . Araújo, Diana; Martins, Matilde; Concórdio-Reis, Patrícia; Roma-Rodrigues, Catarina; Morais, Maria; Alves, Vítor D.; Fernandes, Alexandra R.; Freitas, Filomena; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; DCV - Departamento de Ciências da Vida; DCM - Departamento de Ciência dos Materiais; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); Molecular Diversity Preservation International (MDPI)
FucoPol, a fucose-rich polyanionic polysaccharide, was used for the first time for the preparation of hydrogel membranes (HMs) using Fe3+ as a crosslinking agent. This study evaluated the impact of Fe3+ and FucoPol concentrations on the HMs’ strength. The results show that, above 1.5 g/L, Fe3+ concentration had a limited influence on the HMs’ strength, and varying the FucoPol concentration had a more significant effect. Three different FucoPol concentrations (1.0, 1.75 and 2.5 wt.%) were combined with Fe3+ (1.5 g/L), resulting in HMs with a water content above 97 wt.% and an Fe3+ content up to 0.16 wt.%. HMs with lower FucoPol content exhibited a denser porous microstructure as the polymer concentration increased. Moreover, the low polymer content HM presented the highest swelling ratio (22.3 ± 1.8 g/g) and a lower hardness value (32.4 ± 5.8 kPa). However, improved mechanical properties (221.9 ± 10.2 kPa) along with a decrease in the swelling ratio (11.9 ± 1.6 g/g) were obtained for HMs with a higher polymer content. Furthermore, all HMs were non-cytotoxic and revealed anti-inflammatory activity. The incorporation of FucoPol as a structuring agent and bioactive ingredient in the development of HMs opens up new possibilities for its use in tissue engineering, drug delivery and wound care management.
Unidades organizacionais
Descrição
Palavras-chave
Contribuidores
Financiadores
Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
Número da atribuição
SFRH/BD/140829/2018