Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications

Abstract

In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting.

Keywords: carrageenan; drug delivery; fucoidan; macrophage targeting; sulfated polysaccharides; ulvan.

Figure 1

Number of scientific publications published on the topic “name of polymer” and “drug delivery” as a function of publication years. Taken from ISI Web of Knowledge. The colors allude to the colors of algae (red: carrageenan, brown: fucoidan, green: ulvan).

Figure 2

Carrageenan structures. Linear chains of repeating galactose units in d configuration and 3,6-anhydro-galactose copolymer, joined by alternating α-(1→3) and β-(1→4) glycosidic linkages.

Figure 3

Scheme of carrageenan gel formation. The structure of κ- and ι-carrageenan allows segments of the two molecules to form the so-called double helices which bind the chain molecules in a three-dimension network. The associated counterions such as Na⁺, K⁺ and Ca²⁺, are also required to induce the sol-gel transition of the referred types of carrageenan.

Figure 4

Scheme of α-l-fucose chains observed in fucoidans isolated from several algae belonging to the taxonomic orders Chordariales and Laminariales (a) and Fucales (b); (a) The chain is only composed of repeating (1→3)-linked α-l-fucose residues; (b) The chain consists of alternating (1→3)- and (1→4)-linked α-l-fucose residues. R represents the positions of potential attachment of carbohydrate residues (glucuronic acid, mannose, galactose, xylose, α-l-fucose, fucoside) and non-carbohydrate (sulfate and acetate) substituents.

Figure 5

Structure of the main repeating disaccharides in ulvan isolated from Ulva sp. (a) Ulvanobiuronic acid type A3s disaccharide is composed of glucuronic acid and sulfated rhamnose, whereas type B3s consists of iduronic acid and sulfated rhamnose; (b) Ulvanobiose acids in which xylose or sulfated xylose residues occur in place of uronic acids.

Figure 6

Calu-3 and A549 cell viability measured by the methyltetrazolium (MTT) assay after 24 h of exposure to chitosan/carrageenan nanoparticles. Data represent mean ± SEM (n = 6). Adapted with permission from [163].

Figure 7

Lipopolysaccharide-induced RAW 264.7 cells detected by flow cytometry. Data are mean ± SD of values calculated on 5 distinct batches (n = 5). Statistical analysis was performed by one-way ANOVA. * p < 0.01 versus control. *** p < 0.001 versus control. ### p < 0.001 versus LPS. Adapted with permission from [207].

Figure 8

The release kinetics of basic fibroblast growth factor (bFGF) from chitosan/fucoidan nanoparticles, as measured by ELISA. Adapted with permission from [240].