title: Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics.
abstract: Top-down microfabrication techniques were used to create silicon-based membranes consisting of arrays of uniform channels having a width as small as 7 nm. The measurement of diffusion kinetics of solutes across these membranes under sink conditions reveals non-Fickian behavior as the nanopore width approaches the hydrodynamic diameter of the solute. Zero-order diffusion of interferon is observed at channel width of 20 nm, and the same phenomenon occurs with albumin and 13-nm-wide channels, whereas Fickian diffusion kinetics is seen at 26 nm and larger pore sizes. A prototypical drug delivery device is described that is fitted with a 13-nm nanopore membrane and loaded with radio-labeled BSA. Following subcutaneous implantation in rats, diffusion from the device provided prolonged levels of BSA in the blood. Such a nonmechanical device offers important advantages in drug delivery applications, including zero-order release and high loading capacity.
authors.affiliation: iMEDD Inc., Columbus, OH, USA. fmartin@imeddinc.com
authors.forename: Frank
authors.initials: F
authors.lastname: Martin
authors.forename: Robbie
authors.initials: R
authors.lastname: Walczak
authors.forename: Anthony
authors.initials: A
authors.lastname: Boiarski
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen
authors.forename: Teri
authors.initials: T
authors.lastname: West
authors.forename: Carlo
authors.initials: C
authors.lastname: Cosentino
authors.forename: John
authors.initials: J
authors.lastname: Shapiro
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D002417:Cattle; D004058:Diffusion / Q000187:drug effects; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics; D036103:Nanotechnology / Q000295:instrumentation* / Q000379:methods*; D010316:Particle Size; D051381:Rats; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine