Rheological, thermal and spectroscopical properties of the macromolecular complex between sodium hyaluronate and cisplatin for anticancer chemotherapy

Hyaluronic acid and its sodium salt (sodium hyaluronate; hyaluronan; NaHA) are widely used for drug delivery. Here, a thin film of high molecular weight NaHA with the anticancer agent cisplatin (cisPt) was prepared to deliver the drug loco-regionally on the pleura after tumor resection. For preparing films, NaHA, cisPt, and excipients were dissolved in water; the resulting viscous film-forming mixture (FFM) was cast into wet films and dried. It was discovered that a cisPt/NaHA complexation in films was responsible for the observed higher drug efficacy from films. Here, we investigated the rheological, thermal and spectroscopical properties of the cisPt/NaHA complex. The size exclusion chromatography (SEC) showed a unimodal molecular weight distribution of NaHA in aqueous solution. The viscosity of FFM increased with increasing cisPt concentration, indicating cross-linking due to cisPt/NaHA complexation. In DSC analysis, the water evaporation temperature of both FFM and film decreased due to cisPt/NaHA complexation, suggesting that the complexation with Pt2+ displaced water molecules originally bound to NaHA. FTIR-ATR spectral changes in cisPt-loaded vs. placebo films suggested that complexation involved the carboxylate groups of the polysaccharide. Finally, energy dispersive spectroscopy coupled with SEM demonstrated that the cisPt/NaHA complex in films appeared to be a network of aggregates.