title: Evaluation of drug interactions with nanofibrillar cellulose.
abstract: Nanofibrillar cellulose (NFC) (also referred to as cellulose nanofibers, nanocellulose, microfibrillated, or nanofibrillated cellulose) has recently gotten wide attention in various research areas and it has also been studied as excipient in formulation of the pharmaceutical dosage forms. Here, we have evaluated the interactions between NFC and the model drugs of different structural characteristics (size, charge, etc.). The series of permeation studies were utilized to evaluate the ability of the drugs in solution to diffuse through the thin, porous, dry NFC films. An incubation method was used to determine capacity of binding of chosen model drugs to NFC as well as isothermal titration calorimetry (ITC) to study thermodynamics of the binding process. A genetically engineered fusion protein carrying double cellulose binding domain was used as a positive control since its affinity and capacity of binding for NFC have already been reported. The permeation studies revealed the size dependent diffusion rate of the model drugs through the NFC films. The results of both binding and ITC studies showed that the studied drugs bind to the NFC material and indicated the pH dependence of the binding and electrostatic forces as the main mechanism.
authors.affiliation: Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address: ruzica.kolakovic@helsinki.fi.
authors.forename: Ruzica
authors.initials: R
authors.lastname: Kolakovic
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Antti
authors.initials: A
authors.lastname: Laukkanen
authors.forename: Maarit
authors.initials: M
authors.lastname: Hellman
authors.forename: Päivi
authors.initials: P
authors.lastname: Laaksonen
authors.forename: Markus B
authors.initials: MB
authors.lastname: Linder
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
mesh_terms: D000284:Administration, Oral; D002151:Calorimetry; D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004058:Diffusion; D004347:Drug Interactions; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000737:chemistry; D017274:Nafarelin / Q000737:chemistry; D057139:Nanofibers / Q000737:chemistry*; D016062:Porosity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012995:Solubility; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics; D014990:Xylans / Q000737:chemistry
chemical_list: D005079:Excipients; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014990:Xylans; D017274:Nafarelin; D002482:Cellulose; D009113:Muramidase
keywords: Binding capacity; Drug binding; Drug permeation; ITC; Incubation; NFC films; Nanofibrillar cellulose