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触发产气的微囊用于快速可控药物释放

发布时间:2018-02-12 05:50

  本文关键词: IR780 全氟己烷 快速可控 微囊 胶原蛋白 出处:《南京大学》2014年硕士论文 论文类型:学位论文


【摘要】:近年来,高分子聚合物PLGA已经被广泛地用于抗肿瘤药载药系统的研究与应用中。作为一种理想的药物载体,PLGA具有良好的生物相容性、生物可降解性以及合适的相转变温度。但是,常温下PLGA聚合物链之间交联较为紧密,使所载药物难以释放出来。载体中药物的缓慢释放使肿瘤细胞周围药物浓度往往达不到将其杀灭的阈值,因此导致对肿瘤细胞增值的抑制效果较差。本文设计了一种新型药物递送系统,该系统可以在近红外激光触发下短时间内释放出大量所载药物。该系统是一种新型的载药PLGA复合微囊,广谱抗肿瘤药物阿霉素(doxorubicin,DOX)和近红外染料IR-780被均匀分散于微囊疏水性的PLGA壳层中,而液态全氟己烷(PFH)被包裹在微囊核中。当用近红外激光照射后,由于IR-780的存在,微囊及其周围溶液温度快速升高,包裹在微囊中的液态全氟己烷气化使微囊体积膨胀甚至引起微囊壳层破裂,微囊壳层中的阿霉素被快速大量地释放出来。同时,高温使PLGA链之间的交联变得松散也会促进阿霉素的释放。在肿瘤细胞悬液中加入该微囊,并定时用近红外激光照射后,肿瘤细胞的存活率明显降低,微囊表现出了良好的细胞毒效应。该微囊能够克服以PLGA为载药材料的药物递送系统中所载药物释放缓慢的缺点,是一种有应用潜力的快速可控释药载体。胶原蛋白具有良好的生物相容性及低免疫原性,近年来胶原蛋白被广泛地应用于组织工程、医疗器械以及载药系统中。本文研究了从新鲜猪皮中提取和纯化Ⅰ型胶原蛋白的方法,并用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和傅里叶变红外光谱(FTIR)对所提胶原进行了分析鉴定,证明了所制备的胶原蛋白为Ⅰ型。
[Abstract]:In recent years, polymer PLGA has been widely used in the research and application of anti-tumor drug delivery system. As an ideal drug carrier, PLGA has good biocompatibility. Biodegradability and appropriate phase transition temperature. However, the cross-linking of PLGA polymer chains is relatively close at room temperature. The slow release of drugs in the carrier often causes the concentration of drugs around tumor cells to fail to reach the threshold to kill them, As a result, the inhibition of tumor cell proliferation was poor. A novel drug delivery system was designed in this paper. The system can release a large amount of drugs under the trigger of near infrared laser in a short time. The system is a new drug loaded PLGA composite microcapsule. The broad-spectrum antitumor drug doxorubicindox) and the near infrared dye IR-780 were uniformly dispersed in the hydrophobic PLGA shell of the microcapsules, while the liquid perfluorohexane was encapsulated in the microcapsule nucleus. When irradiated with near infrared laser, the presence of IR-780 was observed. The liquid perfluorohexane encapsulated in the microcapsules expands in volume and even causes the microcapsule shell to rupture, and the adriamycin in the microcapsule shell is released rapidly and in large quantities. The release of adriamycin was also promoted by the loosening of crosslinking between PLGA chains by high temperature. The survival rate of tumor cells was significantly decreased after the microcapsules were added to the suspension of tumor cells and irradiated with NIR laser at regular intervals. The microcapsules exhibit good cytotoxic effects. The microcapsules can overcome the disadvantages of slow release of the drugs contained in the drug delivery system using PLGA as the drug carrier. Collagen has good biocompatibility and low immunogenicity. In recent years, collagen has been widely used in tissue engineering. In medical instruments and drug delivery systems, a method for extracting and purifying collagen type I from fresh pig skin was studied. The extracted collagen was identified by SDS-PAGE and Fourier transform infrared spectroscopy (FTIR). It was proved that the prepared collagen was type 鈪,

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