Electrically Triggered Release of a Small Molecule Drug from a Polyelectrolyte Multilayer Coating

Abstract

Electrically triggered drug delivery represents an attractive option for actively and remotely controlling the release of a therapeutic from an implantable device (e.g., a “pharmacy-on-a-chip”). Here we report the fabrication of nanoscale thin films that can release precise quantities of a small molecule drug in response to application of a small, anodic electric potential of at least +0.5 V versus Ag/AgCl. Films containing negatively charged Prussian Blue (PB) nanoparticles and positively charged gentamicin, a small hydrophilic antibiotic, were fabricated using layer-by-layer (LbL) assembly. When oxidized, the PB nanoparticles shift from negatively charged to neutral, inducing dissolution of the film. Films with thicknesses in the range 100–500 nm corresponding to drug loadings of 1–4 μg/cm2 were characterized. We demonstrate control over the drug dosage by tuning the film thickness as well as the magnitude of the applied voltage. Drug release kinetics ranging from triggered burst release to on/off, or pulsatile release, were achieved by applying different electric potential profiles. Finally, the in vitro efficacy of the released drug was confirmed against Staphylococcus aureus bacteria. Given the versatility of an external electrical stimulus and the ability of LbL assembly to conformally coat a variety of substrates regardless of size, shape, or chemical composition, we maintain that electrically controlled release of a drug from an LbL-coated surface could have applications in both implantable medical devices and transdermal drug delivery systems.

Programmable and on-demand drug release using electrical stimulation

“…Among them, pulsatile drug delivery systems (PDDS) have drawn attention as they allow repeatable and reliable drug release flux for clinical needs. Further, external stimulation signals such as temperature variation, 9,10 magnetic fields, [11][12][13][14] and electric fields, [15][16][17][18][19][20][21] can be used in PDDS to trigger or control drug release rates, thereby allowing remote control of local drug administration. Most of the PDDS devices are composed of a drug-loading container covered with a functional membrane, with drug release rates through the functional membrane controlled by modulating the external stimulations.…”

“…However, both Santini and Chung's micro-reservoir devices are destroyed after use. To amend the problem, Schmidt et al 20 recently fabricated a nanofluidic membrane system then utilized electrokinetic nature of drug molecules to control the magnitude of release rates. These studies show that drug release modulation with electrical stimulations is feasible and can behave in a consistent and repeatable manner.…”

Disassembly of redox responsive poly(ferrocenylsilane) multilayers: The effect of blocking layers, supporting electrolyte and polyion molar mass

“…Redox potentials can be controlled in an easy and precise way and can also be employed to provide spatial control over domains with dimensions as thick as the thinnest conducting wires that can be obtained by nanofabrication (i.e., on the order of 10-20 nm) [1]. In addition to many applications as for example, mechanical actuators or sensors, redox responsive polymers can also act as a molecular release medium with tuneable release properties [2,3].…”

Multilayered thin films from poly(amido amine)s and DNA

“…Therapeutic agents to be released are incorporated during multilayer assembly and are subsequently released either via simple diffusion [32], biodegradation of the polyelectrolyte building block [33], or induced by internal [34] or external [35] triggers. In view of cell transfecting surfaces, Lynn and Bechler reported that the two multilayer components (i.e., hydrolysable poly(b-amino ester) and DNA) were found to co-localize within transfected cells cultured in the vicinity of the surface, indicating that either the polymer-DNA complex is released, or the separate components are released and later form a complex in cell culture medium before being internalized by cells [36].…”