Transdermal delivery systems based on natural polymeric biomaterials

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

Publication . Araújo, Diana; Rodrigues, Thomas; Delgado Alves, Vitor; Freitas, Filomena

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 applications

2022Journal article

Open access

Deacetylation and Desuccinylation of the Fucose-Rich Polysaccharide Fucopol: Impact on Biopolymer Physical and Chemical Properties

Publication . Baptista, Sílvia; Araújo, Diana; Concórdio-Reis, Patrícia; Marques, Ana C.; Fortunato, Elvira; Delgado Alves, Vitor; Freitas, Filomena

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 ºC 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 Young0s 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

2022Journal article

Open access

Novel Hydrogel Membranes Based on the Bacterial Polysaccharide FucoPol: Design, Characterization and Biological Properties

Publication . Araújo, Diana; Martins, Matilde; Concórdio-Reis, Patrícia; Roma-Rodrigues, Catarina; Morais, Maria; Delgado Alves, Vitor; Fernandes, Alexandra; Freitas, Filomena

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.

2023-07Journal article

Open access

Chitin-Glucan complex hydrogels: physical-chemical characterization, stability, in vitro drug permeation, and biological assessment in primary cells

Publication . Araújo, Diana; Rodrigues, Thomas; Roma-Rodrigues, Catarina; Alves, Vitor D.; Fernandes, Alexandra R.; Freitas, Filomena

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 g/cm2/h) and salicylic acid (19.53 g/cm2/h), compared to ibuprofen sodium and diclofenac sodium (4.26 and 0.44 g/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.

2023-02Journal article

Open access