Optimized loading and sustained release of hydrophilic proteins from internally nanostructured particles

In this study, we demonstrate that emulsified microemulsions and micellar cubosomes are suitable as sustained delivery vehicles for water-soluble proteins. Through structural modifications, the loading efficiency of two model proteins, namely bovine serum albumin (BSA) and cytochrome c could be remarkably increased. A procedure for preparing these particles loaded with optimized amounts of sensitive substances is presented. Loading and dispersion at low temperatures is performed in two successive steps. First, a water-in-oil microemulsion is loaded with the proteins. Subsequently, this phase is dispersed in water resulting in particles with microemulsion and micellar cubic internal structure and a size of approximately 620 nm. This two-step method ensures optimal loading of the particles with the proteins. These nanostructured particles are able to sustain the release of the water-soluble BSA and cytochrome c. Within one day, less than 10% of BSA and 15% of cytochrome c are released. The release rate of cytochrome c is influenced by the nanostructure of the particles.