The idea of this study was to combine hyaluronic acid (HA) viscosupplementation and a local/controlled delivery of a hydrophobic anti-inflammatory drug. To this aim, we investigated the ability of an octenyl succinic anhydride (OSA) modified HA (OSA-HA), to act as a solubility enhancer and as a platform for slow release of hydrophobic drug(s). This novel HA derivative could act as a viscosupplementation agent and, for this reason, a rheological study was conducted along with calorimetric analysis. Differential scanning calorimetry (DSC) results revealed that the ability of HA to sequester water is enhanced by the introduction of lipophilic functions within HA molecules, resulting in a decrease of the fraction of free water able to freeze compared to the unmodified HA. Moreover, OSA-HA solutions appear to be an appropriate tool to be used in viscosupplementation therapy owing to their suitable viscoelastic features. Our results indicate that OSA-HA is able to self-assemble into micelles, load a hydrophobic drug and release the active molecule with controlled kinetics. In particular, the analysis of release profiles showed that, in all cases, drug diffusion into the gel is faster compared to gel/drug dissolution, being the dissolution contribution more relevant as the OSA-HA concentration increases.
Keywords: Amphiphilic polymers; Drug delivery; Hyaluronic acid; Hydrophobic drug; Micelles; Viscoelastic properties; Viscosupplementation.
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