Target-specific drug delivery and molecular imaging systems based on hyaluronic acid = 히알루론산을 이용한 표적 특이성 약물 전달 및 분자영상 시스템

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Novel hyaluronic acid (HA) nanogels physically encapsulating small interfering RNA (siRNA) was fabricated by an inverse water-in-oil emulsion method. Thiol-conjugated HA dissolved in aqueous emulsion droplets was ultrasonically crosslinked via the formation of disulfide linkages to produce HA nanogels with a size distribution from 200 to 500 nm. Green fluorescence protein (GFP) siRNA was physically entrapped within the HA nanogels during the emulsion/crosslinking process. The HA/siRNA nanogels were readily taken up by HA receptor positive cells (HCT-116 cells) having HA-specific CD44 receptors on the surface. Release rates of siRNA from the HA nanogels could be modulated by changing the concentration of glutathione (GSH) in the buffer solution, indicating that the degradation/erosion of disulfide crosslinked HA nanogels, triggered by an intracellular reductive agent, controlled the release pattern of siRNA. When HA nanogels containing GFP siRNA were co-transfected with GFP plasmid/Lipofectamine to HCT-116 cells, a significant extent of GFP gene silencing was observed in both serum and non-serum conditions. The gene silencing effect was reduced in the presence of free HA in the transfection medium, revealing that HA nanogels were selectively taken up by HCT-116 cells via receptor mediated endocytosis. Chemical conjugates of paclitaxel and hyaluronic acid (HA) were synthesized by utilizing a novel HA solubilization method in a single organic phase. Hydrophilic HA was completely dissolved in anhydrous DMSO with addition of polyethylene glycol (PEG) by forming nano-complexes. Paclitaxel was then chemically conjugated to HA in the DMSO phase via an ester linkage without modifying extremely hydrophilic HA. A series of HA-paclitaxel conjugates with different conjugation percents were synthesized and characterized. HA-paclitaxel conjugates self-assembled in aqueous solution to form nano-sized micellar aggregates, as characterized by dynamic light scattering (DLS), a...
Park, Tae-gwanresearcher박태관researcher
한국과학기술원 : 생명과학과,
Issue Date
309254/325007  / 020055122

학위논문(박사) - 한국과학기술원 : 생명과학과, 2009.2, [ xiv, 126 p. ]


hyaluronic acid; drug delivery; molecular imaging; 히알루론산; 약물 전달; 분자 영상; hyaluronic acid; drug delivery; molecular imaging; 히알루론산; 약물 전달; 분자 영상

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