Self-assembling alginate-based diblock polymers

Abstract

Polysaccharides are an abundant, diverse, and naturally occurring class of biopolymers. Alginate is a marine polysaccharide from brown algae and some bacterial species. Industrially, alginates are widely applied for the production of pharmaceuticals and food. Many of the applications rely on the gel-forming properties of alginate in the presence of calcium. While alginate microcapsules have been extensively explored for cell encapsulation, alginate nanoparticles have been minimally described. This is primarily because of challenges related to their preparation and stability.

Diblock polymers are a class of block copolymers where two blocks are linearly linked, forming a new macromolecule. Self-assembling amphiphilic diblock polymers have been used for the preparation of nanosized morphologies such as micelles, vesicles, and membranes. While diblock polymers have been extensively described in the field of polymer chemistry, only a few examples of diblock polymers comprised solely of polysaccharides exist. In this work, alginate was incorporated in diblock polysaccharides, and the properties of the diblock polymers were studied in the presence of some divalent cations (Ca2+, Sr2+, and Ba2+).

Alginate-based diblock polymers were obtained by reacting the alginate reducing end with dioxyamine and dihydrazide linkers. The method was used to prepare a library of oligoguluronate-b-dextran (Gn-b-Dexm) diblock polymers. The reducing end protocols developed were additionally employed for the incorporation of azides or alkynes, which subsequently allowed for the use of Cu-mediated or Cu-free azide-alkyne Huisgen cycloaddition to prepare block structures.

The solution properties of the Gn-b-Dexm diblocks were studied in the presence of Ca2+ delivered by diffusion using a dedicated dialysis cell. For certain combinations of chain lengths, well-defined nanoparticles could be prepared. The particles were of micellar type, with a Ca2+ complexed oligoguluronate core, and a stabilizing dextran corona. The particles were characterized by different scattering techniques, revealing a narrow size distribution, and a radius of gyration below 10 nm. The particles could be visualized by AFM, confirming a spherical shape. Additionally, self-assembly with Sr2+and Ba2+ could give nanoparticles of similar type only with a slightly smaller size.

The nanoparticles prepared by Ca2+-induced self-assembly of Gn-b-Dexm were demonstrated to be stable over time, both in water and in CaCl2. Their small size and high stability make them attractive for several applications. Alginate-based diblock polymers represent a new class of alginate biomaterials, allowing for the preparation of alginate-based nanoparticles. In the future, a range of interesting combinations of polysaccharides can be envisioned, adding to this new class of engineered polysaccharide-based materials.