title: Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices--enhanced stability and release.
abstract: 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.
authors.affiliation: Division of Pharmaceutical Technology, P.O. Box 56, FI-00014, University of Helsinki, Finland. hanna.valo@helsinki.fi
authors.forename: Hanna
authors.initials: H
authors.lastname: Valo
authors.forename: Miia
authors.initials: M
authors.lastname: Kovalainen
authors.forename: Päivi
authors.initials: P
authors.lastname: Laaksonen
authors.forename: Merja
authors.initials: M
authors.lastname: Häkkinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Markus
authors.initials: M
authors.lastname: Linder
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood; D001665:Binding Sites; D002482:Cellulose / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005612:Freeze Drying; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D005658:Fungi / Q000737:chemistry / Q000378:metabolism; D055767:Immobilized Proteins; D017964:Itraconazole / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005656:Fungal Proteins; D055767:Immobilized Proteins; D011994:Recombinant Proteins; D017964:Itraconazole; D002482:Cellulose