Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics

J Control Release. 2005 Jan 20;102(1):123-33. doi: 10.1016/j.jconrel.2004.09.024.

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.

MeSH terms

  • Animals
  • Cattle
  • Diffusion / drug effects
  • Drug Delivery Systems / instrumentation*
  • Drug Delivery Systems / methods*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / pharmacokinetics
  • Nanotechnology / instrumentation*
  • Nanotechnology / methods*
  • Particle Size
  • Rats
  • Recombinant Proteins
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / pharmacokinetics

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Serum Albumin, Bovine