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A simple approach is reported to engineer biodegradable and biocompatible nanoporous hyaluronic acid particles (NPHAs) with a characteristic sponge-like morphology and uniform size. These NPHAs can be synthesized using the concomitant cross-linking of hyaluronic acid and the cross-linking agent precipitation. The nanoporous architecture of NPHAs prevents the rapid enzymatic degradation of hyaluronic acid and controls the erosion of microparticles in physiological conditions. Once injected into an intra-articular body cavity of healthy mice, these NPHAs reside at the point-of-delivery for an extended time period, exhibiting a sustained release of hyaluronic acid. In addition, in vivo studies indicate the persistence of NPHAs in the knee joints with neither accumulation into major organs, nor any local or systemic side-effect. The use of NPHAs is emphasized as reservoirs of hyaluronic acid, effectively providing an innovative and safe platform for prolonging the favorable effects displayed by hyaluronic acid on joints affected by osteoarthritis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]