Optimization of spray-dried hyaluronic acid microspheres to formulate drug-loaded bone substitute materials

We present here our first results concerning the evaluation of hyaluronic acid (HA) as a candidate to formulate an organic–mineral cement with sustained release properties. Incorporating drug-loaded microspheres in mineral bone cements is an alternative strategy to improve their ability as drug delivery materials. To synthesize microspheres according to a reproducible process and control at the same time their morphology and their encapsulation efficiency is one of the main challenges of the conception of such drug-loaded bone substitute. In this context, we investigated the potentialities of two HA, differing by their molecular weight, to form microspheres by a spray-drying technique. Erythrosin B (EB) was encapsulated as a model drug and spray-drying process conditions were optimized. To perform this, the rheological behavior and viscosity of HA solutions have been related to their spray-drying ability, and then to the resulting microparticles morphological properties and size distribution. Reproducible microspheres, answering to the requirements in terms of size and encapsulation efficiency, have been obtained from both HA. However the HA exhibiting the lowest molecular weight, HA600, led to smaller microparticles, with a higher polydispersity index. Their swelling ability, related to their stability upon rehydration, also appeared reduced. In this context, HA850, with the highest molecular weight, was selected and the possibility to modulate drug release by HA850 microspheres incorporation into a mineral cement was explored. EB release kinetics from HA microspheres, HA microspheres loaded cement and reference cement were followed at 37 °C, in Tris buffer at pH 7.4, using European Pharmacopoeia flow-through cells. Results showed that HA microspheres incorporation into a mineral cement permitted to modify the cement drug release profile and led to a sustained release.