Controlled release carriers of growth factors FGF-2 and TGFbeta1: synthesis, characterization and kinetic modelling.

The purpose of this work is to produce microspheres loaded with transforming growth factor beta1 TGFbeta1 and basic fibroblast growth factor FGF-2; to ensure the protein protection from degradation during the encapsulation and storage steps, to evaluate the release rate and the microspheres toxicity. The water in oil in water double emulsion technique was adapted to avoid the protein degradation during the encapsulation. The obtained microspheres were deeply characterized to evaluate their size, morphology, toxicity, the way of degradation, the protein stability and release rate. The microspheres were found to be biocompatible and the encapsulation efficiency was about 35%. It was observed that the obtained microspheres increase the shelf life of the growth factors. The diffusion coefficient was quantified using Fick's law of diffusion that was combined to an empirical equation representing the decrease in the protein stability. Such modelling helped to give indirect information about the microspheres morphology and drug distribution within the microspheres. The main conclusion consists of the formation of a higher compact polymer matrix when smaller particles are produced, which has different distinct effects: the encapsulation efficiency and the stability of the encapsulated growth factor are enhanced while both the growth factor diffusion and the polymer degradation rates decrease.