title: Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane.
abstract: General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (≤1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (≤1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others.
authors.affiliation: Nanomedicine Department, Houston Methodist Research Institute (HMRI), Houston, TX, USA. agrattoni@houstonmethodist.org.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bruno
authors.forename: Thomas
authors.initials: T
authors.lastname: Geninatti
authors.forename: R Lyle
authors.initials: RL
authors.lastname: Hood
authors.forename: Daniel
authors.initials: D
authors.lastname: Fine
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scorrano
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schmulen
authors.forename: Sharath
authors.initials: S
authors.lastname: Hosali
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grattoni
mesh_terms: D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000528:radiation effects; D050091:Dendrimers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004574:Electromagnetic Fields; D004867:Equipment Design; D019544:Equipment Failure Analysis; D037741:Fullerenes / Q000008:administration & dosage* / Q000737:chemistry* / Q000528:radiation effects; D007700:Kinetics; D008567:Membranes, Artificial; D008839:Microelectrodes
chemical_list: D003692:Delayed-Action Preparations; D050091:Dendrimers; D037741:Fullerenes; D008567:Membranes, Artificial