Reducing Passive Drug Diffusion from Electrophoretic Drug Delivery Devices through Co-Ion Engineering.

Shao-Tuan Chen,Esther Udabe,Liliana C Tomé,George G Malliaras,David Mecerreyes,Robert R Mcleod,Megan N Renny,Christopher M Proctor,Elise P W Jenkins,Jorge L Olmedo-Martínez

doi:10.1002/advs.202003995

Abstract

Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion‐conducting membrane out to the local implanted area. This solvent‐flow‐free “dry” delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co‐ion is presented. By switching acetylcholine's associated co‐ion from chloride to carboxylate co‐ions as well as sulfopropyl acrylate‐based polyanions, steady‐state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices.

Highlights

Further numerical simulations demonstrate the applicability and consistent leakage reduction capability of co-ion engineering to a variety of drugs commonly used in electrophoretic drug delivery devices
We demonstrate, drug leakage in ion exchange membrane (IEM) based electrophoretic drug delivery devices can be suppressed without affecting the active device performance by changing the associated co-ion in the drug solution
We show that the steady-state leakage rate of acetylcholine can be reduced up to sevenfold by changing its associated co-ion from chloride or carboxylates of increasing alkyl chain length (C4 to C8) to poly(sulfopropyl acrylate)

Summary

Drug Transport Mechanisms in an Electrophoretic Drug Delivery Device

An electrophoretic drug delivery device consists of a source drug reservoir with a source electrode, an ion exchange membrane (IEM) at the point of drug delivery and a target electrode in contact with the target site (e.g., tissue area immediately external to the implant) (Figure 1a). In a standard electrophoretic drug delivery device, the high drug activity gradient at the IEM-target interface drives drug out of the membrane and into the target where it is typically metabolized or transported away via convection.[29,30] The continued loss of drug creates a concentration gradient dC in the membrane, and dx this concentration gradient is due to an irreversible thermodynamic process, regardless of the presence of an external voltage Reducing this concentration gradient has been the focus of previous reports aiming to limit drug leakage.[15,31] these approaches introduce additional power consumption due to increased ionic resistance. With this theoretical basis in mind, we conducted a series of experiments to measure the effect of co-ions on drug leakage

Drug Leakage Profile When Paired with Co-Ions of Similar Molecular Weight

Discussion and Conclusion

Experimental Section

Data Availability Statement