Evaluation of hyaluronan as a vehicle for peptide growth factors

Abstract

Sodium hyaluronate, or hyaluronan (HA), was investigated as a vehicle for high molecular weight drugs given subcutaneously. Human recombinant insulin-like growth factor-I (hIGF-I), a peptide showing diverse anabolic cellular effects, was dissolved in different concentrations (0.0–2.0%) of hyaluronan. Three kinds of experiments were performed: a diffusion study, an in vitro release study and an in vivo release study in the rat. The diffusion study showed the diffusion rate of the peptide to be extremely low in hyaluronan, indicating an interaction between vehicle and drug. The in vitro release study showed that the release rate of hIGF-I from the vehicle is dependent on the vehicle concentration; the higher the concentration of hyaluronan the lower the release rate. This result was confirmed in the in vivo release study, where the dorsal rat hind foot was injected with 125I-labelled hIGF-I dissolved in vehicles containing 0.0, 0.5, 1.0 or 2.0% hyaluronan, followed by determination of remaining radioactivity at the injection site. We conclude that HA, a substance which occurs naturally in the body, can retard the release of peptide growth factors.