A Magnetically Triggered Membrane for Drug Delivery

Delivery devices that allow remote, repeatable, and reliable switching of drug flux could have a marked impact on the treatment of a variety of medical conditions. An ideal device for on-demand drug delivery should safely contain a large quantity of drug, release little or no drug in the “off” state, be repeatedly switchable to the “on” state without mechanically disrupting the device, and be triggered noninvasively to release a consistent dosage demanded by a patient (e.g., local pain relief) or prescribed by a doctor (e.g., localized chemotherapy).

Despite the clear clinical need, few such drug delivery devices have been developed and none are available for clinical use. Existing technologies are particularly limited by their inability to be effectively triggered in vivo in the absence of a local implanted heat source, their lack of reproducible release over multiple thermal cycles, their slow response times to stimuli, and/or their inability to dynamically adjust drug dosing according to patient needs. Currently, no existing device overcomes all of these limitations. For example, radio-frequency-activated microchips containing drug-filled reservoirs can achieve rapid on-demand drug delivery but deliver only fixed doses of drug and require implanted electronics. Near-IR responsive nanoparticles consisting of mixtures of PNIPAM and gold-gold sulfide nanoshells can release proteins on demand but deliver inconsistent doses upon multiple triggering cycles.

Ferrofluid-loaded polymer sheets, liposomes, microspheres, microcapsules and nanospheres can be activated remotely by magnetic induction but typically achieve either single burst release events or inconsistent dosing over multiple thermal cycles due to the use of mechanical disruption of the drug-polymer matrix as the flux triggering mechanism. Hence, alternative technologies are needed.

Hydrogels based on thermosensitive poly(N-isopropylacrylamide) (PNIPAM) have been frequently used in triggerable devices. With heating, PNIPAM undergoes a reversible discontinuous phase transition in water, switching from hydrophilic to hydrophobic.

In a PNIPAM-based hydrogel, this phase transition induces a deswelling response which typically reduces drug flux from the hydrogel. Alternately, when PNIPAM is used to fill the pores of a membrane, the pores are opened upon heating as the entrapped polymer shrinks, increasing drug flux through the membrane. Such membranes have been designed by grafting poly(N-isopropylacrylamide) to existing membrane networks5 or by entrapping PNIPAM microgels within a membrane matrix.

However, existing PNIPAM-based devices would be permanently “on” at physiological temperature (37 °C) since their transition temperatures are ∼32 °C. Existing technologies would also require use of an implanted heating system for effective in vivo activation.

New composite membranes based on multiple engineered smart nanoparticles should be capable of rapid, repeatable, and tunable drug delivery upon the application of an external oscillating magnetic field.