软脂酸三甲基壳聚糖聚合物包载去氢骆驼蓬碱肝肿瘤靶向自组装胶束分析-药剂学专业论文.docxVIP

Study on the novel liver cancer targeting self-assembled micelles of harmine based onpalmitoyl-trimethyl-chitosan AbstractObjective: To synthesize three novel amphiphilic polymers including palmitic-trimethyl-chitosan 1 and 2 (TPCS1 and TPCS2), and lactobionic acid modified palmitic-trimethyl-chitosan 2 (Lac-TPCS2) based on trimethyl-chitosan, which can all self-assemble into micelles. What’s more, three drug-loaded micelles (TPCS1/HM, TPCS2/HM, and Lac-TPCS2/HM) can be prepared using the insoluble drug harmine (HM) as a model drug, which can be solubilized by the hydrophobic core of three polymers. Effective delivery of HM to liver tumor part in vivo can be obtained from the targeting effect of polymers and the neurotoxicity of HM can also be reduced because of the sustained release from micellar core, which can increase HM’s antitumor effect of liver carcinoma as a result.Methods: (1) Trimethyl-chitosan was synthesized with alkylated methods, followed by condensation method to synthesis TPCS1, TPCS2 and Lac-TPCS2. Three polymers were then characterized by infrared spectroscopy and 1HNMR before the determination of the critical micelle concentration (CMC) with fluorescence spectrometer. Using TPCS2 as an example, HM loaded micelles were prepared with the film dispersion method and the prescription process was optimized by univariate and central composite design. HM loaded micelles were characterized by several means such as infrared spectroscopy, the release characteristics were then investigated under different media. (3) The human-derived livercancer cell lines，HepG2 cell was used as an in vitro model, and cytotoxicity of micelleswas investigated using MTT assays. And assumed that the uptake and elimination process of micelles into cells is a first-order dynamic model, the cellular uptake process was also英文提要软脂酸三甲基壳聚糖聚合物包载去氢骆驼蓬碱肝肿瘤靶向自组装胶束研究studied. What’s more, the uptake process and mechanism were explored by a variety of ways including atomic force microscopy,