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.

Fig. 1

Images and schematics of the nDS membrane and electrodes, e, used in this study. (A) Optical image of a laser cut Pt-foil electrode. (B) nDS membrane with e-beam deposited Pt electrodes. (C, E, G) Schematics at increasing magnification of an nDS membrane with Pt-foil electrodes epoxied to a silicone gasket, g. (D, F, H) Schematics at increasing magnification of an nDS membrane with deposited Pt electrodes. Nanochannels, nCH, and microchannels, μCH, are indicated. (I) Transmission electron micrograph of a 5.7 nm slit-nanochannel cross-section.

Fig. 2

(A) The structure and properties of DF-1. (B) A schematic of the electrical system adopted for testing, including the nDS membrane with electrodes (a resistor in parallel with a capacitor) and the high-speed reed relay used for applying or discharging the potential using a power supply (left branch) or a discharge resistor (right branch). (C) The waveform of the applied voltage (α = 10 s). (D) Schematics of the custom release testing apparatus. (E) nDS membrane with electron beam deposited electrodes placed onto the polyether ether ketone (PEEK) body of the diffusion testing apparatus. PEEK was used as it is nonconductive. (F) nDS membrane assembly with Pt-foil electrodes, e, and silicon gaskets, s.

Fig. 3

Experimental current-voltage (I–V) results collected with 5.7 nm nanochannel membrane with NaCl at different concentrations. The blue area represents the limiting current region at varying ionic concentration. The graph on the right shows the magnified results for the three lowest concentration. Linear fitting curves are also shown for the estimated ohmic regions. See Supplementary Information (ESI) for direct visual comparison of curves obtained at different ionic concentrations.

Fig. 4

Conductance of NaCl aqueous solution-filled nanochannel membrane as function of the ionic concentration C₀. The dash lines were calculated using equation 2 for the microchannel and the nanochannel. The grey line is a result of the serial addition of both micro- and nano-conductance.

Fig. 5

Schematic of nanochannel Delivery System (nDS) membrane under: (A) ionic concentration polarization (ICP) effect in a slit-nanochannels and (B) electrophoretic effect in a microchannel.

Fig. 6

Cumulative released amount of DF-1 and normalized release rate obtained with the modulation of an applied electrical potential to the electrodes of 5.7 nm (A – C) and 1 μm (D) membranes. Normalized release rates with respect to passive release are shown. Stabilized release rates and rate transients were obtained by linear regression and second-order polynomial interpolation of cumulative release data, respectively. p indicates no potential was applied. The red box in B provides additional support of ICP dominated transport as the application of a symmetric square wave would nullify electrophoretic phenomenon. Both foil (A) and deposited (B – D) Pt electrodes were tested. For clarity, the inset in D displays the experimental curve related to replicate 2. By convention, in our experiments, positive potential and positive bias correspond to the presence of the cathode at the source reservoir side. Calculated passive release curves are also shown for purposes of comparison.