Stimuli-responsive controlled release drug from polymeric devices has been received great attention, as it provides advantages such as better delivery efficiency and site-specific therapy over the conventional routes of drug delivery. By making use of these advantages, a number of studies have been successfully proposed to integrate active drug molecules and host materials, to manipulate drug release desirably. Many previous studies have been reported in response to specific stimuli, such as temperature, 1-3 pH,4,5 electric field,6,7 mechanical signal, 8 and ultrasound. 9 A very recent achievement of a protein-containing hydrogel, reported by Ehrick et al., 10 addressed the stimuli-sensitive hydrogel that can be triggered as a result of the conformational change of the embedded calmodulin protein interacting to bioactive agents. Such a transfer from sensing actuation to mechanical action is novel, but it may be hard for it to reach high accuracy and sensitivity in therapeutic dosing as a burst-controlled drug delivery system. The use of a magnetic field to modulate drug release from polymeric matrices was previously developed. 11-13 Saslawski et al. reported the alginated microspheres for pulsed release of insulin by an oscillating magnetic field. 14 The release rate of insulin from alginate-strontium ferrite microspheres was enhanced in the absence of a magnetic field. Recently, a polyelectrolyte microcapsule embedded with Co/Au used external magnetic fields of 100 -300 Hz and 1200 Oe to increase its permeability to macromolecules. 15 In previous studies, a ferrogel with direct current (dc) magnetic-sensitive properties has been characterized and the amount of drug released from the ferrogel was effectively restricted while applying an external dc magnetic field. 16,17 So far, little investigation has been addressed on the controlled drug release under high-frequency magnetic fields (HFMF). A real-time burst release of drug needs a fast-responsive drug release system to “inject” a precise dose of drug when the body needs it and to “stop” or “slow” the release right after the injection; however, it is hard to easily achieve this with traditional stimuli-responsive hydrogels. A controllable pulsatile-type drug delivery device with repeatable dosing ability in therapeutically effective precision is clinically desirable. Therefore, in this communication, a high-frequency magnetic field (HFMF) triggered pulsatile drug delivery ferrogel with a mechanically reliable and flexible hybrid structure composed of gelatin and magnetic nanoparticles (nanomagnets) of 10-250 nm in diameter is reported. Furthermore, under cyclic exposures to the high-frequency magnetic stimuli, a highly controllable and repeatable burst release with desirable precision from the ferrogels is achieved. Figure 1a illustrates the SEM images of one of the ferrogels shaping in cylindrical geometry, namely 40nm@GE ferrogel, where 40nm@GE represents the ferrogels with gelatin crosslinked with genipin, reinforced by 2 wt % chitosan, and 3% Fe3O4 magnetic nanoparticles (nanomagnets) of average 40 nm in diameter. Chitosan provides several functions in the final hybrid structure, such as (1) matrix for drug encapsulation, (2) materials to provide deformation motion. and (3) binder to link the nanoparticles. As shown, the iron nanoparticles were embedded into the polymer matrix and the nanomagnets displayed a uniform spherical size and dispersed well in the ferrogel. TEM image, i.e., Figure 1b, exhibits that the gelatin * Corresponding authors. Telephone: +886-3-5731818. Fax:+886-35725490; E-mail: (S.-Y.C.) sanyuanchen@mail.nctu.edu.tw; (D.-M.L.) deanmo_liu@yahoo.ca. Figure 1. (a) SEM, (b) TEM, and (c) XPS analyses of ferrogels composed of iron oxide nanoparticles and a gelatin matrix. 6786 Macromolecules2007,40, 6786-6788