The quest for biocompatible drug-delivery devices that could be able to open new administration routes is at the frontier of biomedical research. In this contribution, porous polysaccharide-based microsponges based on crosslinked alginate polymers were developed and characterized by optical spectroscopy and nanoscopic microscopy techniques. We show that macropores with a size distribution ranging from 50 to 120 nm enabled efficient loading and delivery of a therapeutic peptide (CIGB814), presently under a phase 3 clinical trial for the treatment of rheumatoid arthritis. Alginate microsponges showed 80% loading capacity and sustained peptide release over a few hours through a diffusional mechanism favored by partial erosion of the polymer scaffold. The edible and biocompatible nature of alginate polymers open promising perspectives for developing a new generation of polysaccharide-based carriers for the controlled delivery of peptide drugs, exploiting alternative routes with respect to intravenous administration.

Different polysaccharides—namely dextran, carboxymethyl dextran, alginate, and hyaluronic acid—were compared for the synthesis of nanoporous microsponges particles (NMPs) obtained from a one-pot self-precipitation/cross-linking process. The morphologies and sizes of the NMPs were evaluated comparatively with respect to polymer-to-polymer and cross-linker solvents (water-based vs. DMSO). We found that the radial distribution of the polymer in the near-spherical NMPs was found to peak either at the core or in the corona of the particle, depending both on the specific polymer or the solvent used for the formation of NMPs. The NMP porosity and the swelling capability were evaluated via scanning electron microscopy (SEM). The degradation study indicated that after 10 h incubation with a reducing agent, approximately 80% of the NMPs were disassembled into soluble polysaccharide chains. The adsorption and release capacity of each type of NMP were evaluated using fluorescently labeled bovine serum albumin and lysozyme as model proteins, highlighting a release time typically much longer than the corresponding adsorption time. The dependence of the adsorption-release performance on pH was demonstrated as well. Confocal microscopy images allowed us to probe the different distribution of labeled proteins inside the NMP. The safety and non-cytotoxicity of NMPs were evaluated after incubation with fibroblast 3T3 cells and showed that all types of NMPs did not adversely affect the cell viability for concentrations up to 2.25 μg/mL and an exposure time up to 120 h. Confocal microscopy imaging revealed also the effective interaction between NMPs and fibroblast 3T3 cells. Overall, this study describes a rapid, versatile, and facile approach for preparing a universal non-toxic, nanoporous carrier for protein delivery under physiological conditions.