Antibacterial agent formulation and delivery with external triggered release
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Antibacterial agent delivery is of great importance in medicine and dentistry since the bacterial infections are still one of the major reasons for hospitalization and mortality. Despite of the development of technique and pharmacy, more antimicrobial agents are optimized and utilized to treat infections, and their action of principal is better understood which lay a foundation for developing strategies for infection treatment. Over the last decades, many delivery systems have been established to deliver bacterial agents and maintain a sustained activity against them. However, the bacteria are always developing and finding a way to defend themselves. A more responsive antibacterial agent delivery system, which can release the active substances on demand to match the stages of diseases, is highly desirable. Therefore, it motivates us to carry out the work to develop a multifunctional delivery system for antibacterial particle formulation and encapsulation based on the layer-by-layer self-assembly technique and electrospinning, to manipulate the release with external triggers, such as near-infrared (NIR) light and alternating magnetic field (AMF). Strategically, two different kinds of antibacterial agents, chlorhexidine and doxycycline, were studied. Chlorhexidine was fabricated into spherical particles and functionalized with both gold and magnetite nanoparticles, and doxycycline was encapsulated within microcapsules which were also functionalized with magnetite nanoparticles. Their release kinetics and possibilities to trigger the release with either a NIR light or AMF was explored. The first two chapters of the thesis give a general introduction and literature review on the current use of antibacterial agents and the problems concerned, strategies already developed for antibacterial agent delivery, and the potential triggers to induce a smart release. In chapter 3, a brief description of materials and methods, and instruments is presented. Chapter 4 is about chlorhexidine particle formulation. Firstly, particulation of chlorhexidine and mechanism of 4 spherical interconnected structure formation was explored, and then the chlorhexidine particles are encapsulated either by LbL assembly or spray-drying. The chlorhexidine spheres were also functionalized with gold nanorods and Fe3O4 nanoparticles to achieve NIR light and magnetic field manipulated release, and the effect of nanoparticles on the formation of chlorhexidine spheres was also studied. When the chlorhexidine particles were incorporated into electrospun fibers, a sustained antibacterial activity was demonstrated. Chapter 5 is about the delivery of doxycycline to cells with microcapsules and the sustained intracellular doxycycline activity was demonstrated via EGFP expression when the cells were engineered with a tetracycline regulated gene expression system. Intracellular triggered release and upregulation of EGFP expression was achieved by an AMF. The results successfully demonstrated the possibility of chlorhexidine and doxycycline delivery and NIR light/AMF triggered release, which is promising for a future application in medicine and dentistry.
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