title: A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery.
abstract: This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.
authors.affiliation: Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fine
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grattoni
authors.forename: Sharath
authors.initials: S
authors.lastname: Hosali
authors.forename: Arturas
authors.initials: A
authors.lastname: Ziemys
authors.forename: Enrica
authors.initials: E
authors.lastname: De Rosa
authors.forename: Jaskaran
authors.initials: J
authors.lastname: Gill
authors.forename: Ryan
authors.initials: R
authors.lastname: Medema
authors.forename: Lee
authors.initials: L
authors.lastname: Hudson
authors.forename: Milos
authors.initials: M
authors.lastname: Kojic
authors.forename: Miljan
authors.initials: M
authors.lastname: Milosevic
authors.forename: Louis
authors.initials: L
authors.lastname: Brousseau Iii
authors.forename: Randy
authors.initials: R
authors.lastname: Goodall
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D003911:Dextrans; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005947:Glucose; D008567:Membranes, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000295:instrumentation* / Q000379:methods; D010316:Particle Size; D012710:Serum Albumin, Bovine; D013499:Surface Properties
chemical_list: D003911:Dextrans; D008567:Membranes, Artificial; C015219:fluorescein isothiocyanate dextran; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose