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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.
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