The effect of the molecular weight of hyaluronic acid on the physicochemical characterization of hyaluronic acid-curcumin conjugates and in vitro evaluation in glioma cells.

In this study, a redox-sensitive glioma-targeting micelle system was designed to deliver curcumin (CUR) by conjugating it to hyaluronic acid (HA-s-s-CUR, HSC) via disulfide linkage. The effect of the molecular weight of HA on the physicochemical characteristics of HSC conjugates and their in vitro effects in glioma cells were also explored. These conjugates formed nano-scale micelles (209-926 nm) independently in aqueous solution. The micelles greatly increased the solubility of CUR and improved its stability, which is crucial for harnessing the therapeutic potential of this active molecule. The redox sensitivities of different HSC micelles were measured by using a dynamic light scattering method and in vitro release assay, which showed that the low (50 kDa) and medium molecular weight (200 kDa and 500 kD) HA-based conjugates were sensitive to GSH, whereas higher molecular weights (1000 kDa and 2000 kDa) did not show redox-sensitivity. Increased cytotoxicity and uptake of low and medium molecular weight-modified HSC conjugates by the glioma cells further confirmed that the sensitive micelles are more effective for intracellular drug delivery compared to the high molecular weight-modified HSC conjugates or the plain CUR. In summary, the molecular weight of HA affects the physicochemical attributes of HSC conjugates. Only HSC micelles made with HA molecules less than 500 kDa exhibit redox sensitivity.