Nanosizing is an advanced approach to overcome poor aqueous solubility of active pharmaceutical ingredients. One main problem in pharmaceutical nanotechnology is maintaining of the morphology of the nanometer sized particles during processing and storage to make sure the formulation behaves as originally planned. Here, a genetically engineered hydrophobin fusion protein, where the hydrophobin (HFBI) was coupled with two cellulose binding domains (CBDs), was employed in order to facilitate drug nanoparticle binding to nanofibrillar cellulose (NFC). The nanofibrillar matrix provides protection for the nanoparticles during the formulation process and storage. It was demonstrated that by enclosing the functionalized protein coated itraconazole nanoparticles to the external nanofibrillar cellulose matrix notably increased their storage stability. In a suspension with cellulose nanofibrils, nanoparticles around 100 nm could be stored for more than ten months when the specific cellulose binding domain was fused to the hydrophobin. Also freeze-dried particles in the cellulose nanofibrils matrix were preserved without major changes in their morphology. In addition, as a consequence of formation of the immobilized nanodispersion, dissolution rate of itraconazole was increased significantly, which also enhanced the in vivo performance of the drug.