Abstract Body

1. Introduction
We are developing a drug delivery carrier to realize a magnetic drug delivery system (MDDS) that can selectively deliver a drug administered into the body to the target site. MDDS is a treatment system that enables highly efficient drug therapy by increasing the drug concentration at the target site using a magnetic field [1]. In addition, this treatment system is expected to reduce side effects by decreasing the drug concentration that reaches normal tissues. In this study, we proposed magnetic Pickering emulsions (MPEs), which allow the controlled manipulation of particle induction, accumulation, and collapse by the magnetic field, as a new drug carrier for MDDS. Pickering emulsions are emulsions stabilized by solid particles adsorbed at the liquid-liquid interface[2]. Magnetite nanoparticles, which are ferromagnetic solid particles, were used to synthesize MPEs. Furthermore, we quantitatively evaluated the drug release properties of the synthesized MPEs by collapsing them and releasing encapsulated fluorescent substances by applying a magnetic field.

2. Experimental Methods
Magnetite nanoparticles were suspended in distilled water at 10 mg/ml. MPEs were synthesized by homogenizing the prepared magnetite dispersion with soybean oil (Fujifilm Wako Pure Chemicals Corporation) in a ratio of 100:1. To quantitatively evaluate the drug release properties of the synthesized MPEs in a magnetic field, a magnetic field of 1 to 7 T was applied to the MPEs encapsulating the fluorescent substance rhodamine B (Tokyo Kasei Kogyo Co., Ltd., Japan) using a superconducting solenoidal magnet. The amount of rhodamine B released into the aqueous medium by the collapse of the MPEs was measured using a spectrofluorometer (FP-750, JASCO Corp., Japan). The morphological changes of the MPEs and the release behavior of the fluorescent agents before and after the application of the magnetic field were observed using a fluorescence microscope (BX51, OLYMPUS, Japan).

3. Results and Discussion
Fig.1(a) and (c) show the micrographs and fluorescence micrographs of the MPEs before application of magnetic field, and Fig.1(b) and (d) show them after the application of a 3 T magnetic field for 1h. Fig.1(a) shows that the MPEs were uniformly covered with magnetite particles around the oil droplet. Fig.1(b) after the application of magnetic field shows that the MPEs collapsed after the magnetic field was applied. In Fig.1(c), the absence of red fluorescence outside the MPEs suggests that rhodamine B was exclusively encapsulated within the internal phase before the application of the magnetic field. Fig.1(d) after the application of magnetic field shows that red fluorescence was observed on the outside of the collapsed MPEs, while yellow fluorescence was observed on the inside. This indicates that rhodamine B was released into the outer aqueous phase. To quantitatively evaluate the amount of rhodamine B released, fluorescence measurement was employed. The amount of fluorescence increased after the application of magnetic field compared to before the application. This result indicates that the collapse of MPEs increased the release of rhodamine B contained in the MPEs. In addition, there was no significant difference in the amount of rhodamine B released between the application of a 3 T and a 7 T magnetic field. This indicates that the magnetic field at which the magnetite particles reach saturation magnetization is sufficient to promote the collapse of MPEs. These results indicate that the external application of a magnetic field of a few T may be able to collapse the particles and control drug release.

4. Conclusion
MPEs were synthesized as drug delivery carriers for MDDS. To evaluate the drug release properties, particle collapse experiments of MPEs encapsulating rhodamine B were performed using magnetic field. The MPEs collapsed when a magnetic field of 3 T was applied using a superconducting solenoidal magnet. In addition, the release of rhodamine B contained in MPEs increased after the application of a magnetic field due to MPEs collapse. These results indicate that the release of encapsulated material from MPEs can be controlled by a magnetic field. In the future, we plan to clarify the collapse properties of MPEs using magnetic fields through simulations and further experiments.

References

[1] Y. Hirota, M. Chuzawa, F. Mishima, Y. Akiyama, “Development of Magnetic Drug Delivery System Using Superconducting Bulk Magnet” TEION KOGAKU, 45[6], (2010).
[2] Y. Nonomura, “Pickering Emusion”, J. Jpn. Soc. Colour Mater, 89[6], 203-206 (2016).

Acknowledgment

Part of this study was supported by The Naito Foundation.