rhEGF microsphere formulation and in vitro skin evaluation.

An optimized process for protein encapsulation was applied to formulate epidermal growth factor (rhEGF)-poly-epsilon-caprolactone microspheres. Microparticles mean size was 3.8 microm +/- 0.2 and the encapsulation efficiency was 41.9% +/- 2.6. rhEGF recovery after the encapsulation process was approximately 70% (41.9% inside the microspheres and 30% still active in the external phase). In vitro release experiments in McIlvaine buffered solution showed a rhEGF sustained release over 4 days. Skin absorption studies conducted on full-thickness human skin using the Franz cell method showed that 20% rhEGF was released from the microspheres after 24 h exposure. Microspheres accumulated in the stratum corneum where they may act as a rhEGF reservoir. Therefore, rhEGF-PCL microparticles seemed to be promising systems due to their ability to provide locally a sustained release of rhEGF in skin layers.

Improvement of a bovine serum albumin microencapsulation process by screening design.

The first objective of this study was to prepare microspheres containing a model protein by double emulsion-solvent evaporation/extraction method. This method was modified to consider the fragile nature of proteins. These modifications related to the reduction of polymer loss, of agitation duration and of contact time between protein and solvent. The polymer used was poly(epsilon-caprolactone) and the model protein was bovine serum albumin. The control of the microsphere properties constituted a second objective of this project. A screening design methodology was used to evaluate the effects of the process and formulation variables on microsphere properties. Twelve operating factors were retained, and the particle properties considered were the mean size, the encapsulation efficiency, and the surface state. The statistical analysis of the results allowed determining the most influent factors. Considering the whole results, it appeared that the polymer concentration, the osmotic pressure equilibrium and the volume of the inner, outer and organic phases were the most important parameters. Following this screening study, it was possible to produce particles of small size with high entrapment efficiency (near to 80%) and smooth surface. A good batch to batch reproductibility was obtained.