Thermal Responsive Silk Composite Membrane for Magnetic Field Triggered Controllable Drug Delivery

Drug delivery implant which provides localized and controlled drug release is beneficial for the therapies of chronic diseases and tumors. This dissertation aims to develop thermal responsive composite membranes that can be utilized as smart drug release implants. Magnetic field is chosen as the external trigger due to its harmlessness and spatio-temporal control.

A fully biodegradable composite membrane is prepared to prevent the risk of secondary damages caused by surgery to take out non-biodegradable implants after the treatment. The membrane is made from silk fibroin and MNPs, and its stability in water can be prolonged up to several months by increasing the content of ß-sheet structures through ethanol annealing. The thermal degradation of the composite membrane starts consistently at around 200 °C, which is independent of membrane thickness, ethanol post-processing, and the existence of magnetic nanoparticles. The membrane can be remotely triggered by an alternating magnetic field (16 mT, 111 kHz) to open nanopores inside, through which a liquid can then diffuse. The controllable release of the Rhodamine B (Rh.B) model drug is achieved by adjusting the exposure time to the magnetic field. A longer exposure time, which results in more nanopore sites, increases the release rate eventually.

Another composite membrane consisting of silk fibroin, MNPs, and poly(N-isopropylacrylamide) (PNIPAM) microgels (MGs) is prepared to be utilized as on-demand drug delivery implant, which can realize repeated, multiple releases according to the real-time needs of patients. PNIPAM-based thermal and pH dual sensitive microgel particles are fabricated by copolymerization of three monomers including N-isopropylacrylamide, isopropylmethacrylamide, and methacrylic acid. The dried microgels are uniform spheres with core-shell structures, and the diameter is around 1 µm with a core diameter of 800 nm and shell thickness of 160 nm respectively. It has been found that the microgel shrinks when the temperature increases, whereby its volume phase transition temperature (VPTT) depends also on the pH value. Both parameters are adjusted to be in the physiological relevant window. The measured VPTT is around 38 °C at pH 5.0 and increases to 44 °C at pH 7.4.

The controlled release of the Rh.B model drug has been shown by changing the environmental temperature or pH. With higher temperature and more acidic pH, the release rate is faster. Additionally, a higher content of MGs and smaller thickness of the membrane facilitate the release of Rh.B. Furthermore, an alternating magnetic field of 16 mT at 111 kHz is applied to trigger the release of Rh.B remotely. The on/off switching of the magnetic field induces the shrinking/swelling of the microgels, changes reversibly the membrane permeability, and precisely controls the release of the model drug. A control over two orders of magnitude of the release rate (0.01 to 5.0 µg min-1) is achieved by tuning the content of microgels and magnetic nanoparticles, and the thickness of the membrane. In addition, it is found that a higher content of magnetic nanoparticles and a larger thickness contribute to a faster release rate of Rh.B due to the higher heating efficiency. Lastly, the observed much higher release rate of Rh.B in the acidic condition with respect to the physiological one represents a potentially important feature for spatially selective treatment of cancer.

Robust metastable skyrmions and their triangular-square lattice structural transition in a high-temperature chiral magnet

Henrik Moodysson Rønnow, Jonathan White

Skyrmions, topologically protected nanometric spin vortices, are being investigated extensively in various magnets(1-11). Among them, many structurally chiral cubic magnets host the triangular-lattice skyrmion crystal (SkX) as the thermodynamic equilibrium state. However, this state exists only in a narrow temperature and magnetic-field region just below the magnetic transition temperature T-c, while a helical or conical magnetic state prevails at lower temperatures. Here we describe that for a room-temperature skyrmion material(12), beta-Mn-type Co8Zn8Mn4, a field-cooling via the equilibrium SkX state can suppress the transition to the helical or conical state, instead realizing robust metastable SkX states that survive over a very wide temperature and magnetic-field region. Furthermore, the lattice form of the metastable SkX is found to undergo reversible transitions between a conventional triangular lattice and a novel square lattice upon varying the temperature and magnetic field. These findings exemplify the topological robustness of the once-created skyrmions, and establish metastable skyrmion phases as a fertile ground for technological applications.

Nature Publishing Group2016

Magnetic dynamics across the in-field transition in Ca3Co2O6

Nagabhushan Ganesh Hegde, Arnaud Magrez, Henrik Moodysson Rønnow, Ivica Zivkovic

The discovery of multiple coexisting magnetic phases in the crystallographically homogeneous compound Ca3Co2O6 has stimulated ongoing research activity. In recent years the main focus has been on the zero-field-state properties, where exceedingly long timescales have been established. In this study we report a detailed investigation of static and dynamic properties of Ca3Co2O6 across the magnetic field induced transition around 3.5 T. This region has so far been practically neglected, while we argue that in some aspects it represents a simpler version of the transition across the B = 0 state. Investigating the frequency dependence of the ac susceptibility, we reveal that on the high-field side (B > 3.5 T) the response corresponds to a relatively narrow distribution of magnetic clusters. The distribution appears very weakly dependent on magnetic field, with an associated energy barrier of around 200 K. Below 3.5 T a second contribution arises, with much smaller characteristic frequencies and a strong temperature and magnetic field dependence. We discuss these findings in the context of intrachain and interchain clustering of magnetic moments.

AMER PHYSICAL SOC2020