Thermal and pH Sensitive Composite Membrane for On-Demand Drug Delivery by Applying an Alternating Magnetic Field

Implantable drug delivery systems that can realize a scheduled drug release according to the needs of patients would be highly beneficial for the treatment of chronic diseases and cancer. Here, micrometer-sized hydrogel particles with both thermal and pH sensitivities are fabricated for the first time and embedded with magnetic nanoparticles in silk fibroin to generate a composite membrane. The permeability of the membrane is adjustable reversibly by temperature and pH. Promptly responded drug release within 1 min by applying an alternating magnetic field is demonstrated with the membrane. The on/off switching of an alternating magnetic field (16 mT, 111 kHz) induces heat generation by the magnetic nanoparticles resulting in a reversible change of the membrane permeability due to the shrinking/swelling of the microgels. A control over two orders of magnitude of the release rate (0.01-5.0 mu g min(-1)) of Rhodamine B (Rh.B) model drug is achieved by tuning the content of microgels and magnetic nanoparticles, as well as the thickness of the membrane. Additionally, an increase in the release rate of Rh.B in acidic condition with respect to the physiological pH value is demonstrated. This represents an additional functionality of the implantable membrane with relevant features for spatially selective cancer treatment.