【作者】 王哲；

【导师】 井晶； 王振宇；

【作者基本信息】 哈尔滨工业大学 ， 食品科学， 2015， 硕士

【摘要】 化学治疗对肿瘤细胞杀伤能力强,因此作为肿瘤外科手术治疗后的首选治疗手段,但由于用药剂量较大,对人体正常组织细胞易造成伤害。多功能的药物载体具有实现低给药剂量,减少对正常组织损伤等特点。本论文设计并制备了三种具有载有顺铂的磁性药物载体,并对其进行结构表征与载药能力研究。氧化铁磁性纳米粒子的制备及表征:通过化学共沉淀法制备磁性纳米粒子。其观察粒径(DT)约为20 nm,动力学粒径(DV)为78 nm,理论粒径(DS)为16 nm,其饱和磁化强度(Ms)为94 emu/g,该纳米粒子具有较好的结晶性能并具备超顺磁性。CS@MNPs-COO H-CDDP的制备及表征:制备不同浓度壳聚糖包埋磁性纳米粒子,筛选得到形貌稳定,粒径适合的CS@MNPs进行羧化衍生及接枝顺铂。DT约为250 nm,主成分DV为190 nm。包埋及接枝后不影响结晶性,饱和磁化强度(Ms)为43.3 emu/g,顺铂载药量为44.39±3.55%。在p H为7.4时药物载体的顺铂缓释半衰期(t1/2)为18.7 h。24 h和48 h对lovo细胞的IC50值分别为18.5μg/mL和9.8μg/mL。CMCS@MNPs/CDDP的制备及表征:羧甲基化壳聚糖成功包埋磁性纳米粒子并负载顺铂。DT为400 nm,主成分DV为396 nm。饱和磁化强度(Ms)为70.4 emu/g,载药量为49.70±0.12%。在p H为7.4时药物载体的顺铂缓释半衰期(t1/2)为22.4 h。24 h和48 h对lovo细胞的IC50值分别为29.5μg/mL和10.6μg/mL。SiO2@MNPs-COOH-CDDP的制备及表征:二氧化硅包埋磁性纳米粒子,对复合粒子羧基化衍生并接枝顺铂。其DT为200 nm,主成分DV为220 nm,饱和磁化强度(Ms)为26.3 emu/g,载药量为46.15±3.34%。在p H为7.4时药物载体的顺铂缓释半衰期(t1/2)为11.3 h。24 h和48 h对lovo细胞的IC50值为21.4μg/mL和10.2μg/mL。综合考察三种顺铂载体,从各个方面相比较各有优劣,均具备一定的缓释能力及抑癌作用,具有超顺磁性和生物应用前景。更多还原

【Abstract】 In modern medicine, as chemothe rapy has effect on killing tumor cell so be the preferred treatment for cancer after surgical treatment. However, excessive dosage brings damages to normal human cells. The multi- functional drug carrier became a popular research which can overcome over dose and reduce normal tissue damage. This study prepared three kinds of magnetic drug carriers which owned loading capacities of cisplatin, and the structural characterizations and medicine loading capacities were determined.Preparation and characterization of magnetic iron oxide nanoparticles: magnetic nanoparticles were prepared by co-precipitated chemical method. The morphology and distribution of particle size were observed as 20 nm by TEM, the kinetic diameter(Dv) was 78 nm and the theoretical particle size was 16 nm. The substance with the composition of Fe3O4 and Fe2O3.were measured by TGA. The weight percentage(wt)of Fe3O4 was 87.9 %, and wt of Ms(MNPs) was 94 emu/g. The carrier had good crystalline property and superparamagnetic property.Preparation and Characterization of CS@MNPs-COO H-CDDP: Magnetic nanoparticles were embedded by carboxylated derivative chitosan of different concentrations and grafted with cisplatin. The distribution size was about 300 nm, the mean volume particle sizes were 24 and 190 nm. Embedding and surface grafting didn`t affect the crystallinity, Ms was 43.3 emu/g, the wt of magnetic particles was 46.1 %, the paticles loaded 44.39±3.55 % cisplatin. At p H 7.4, cisplatin sustained released drug carrier half- life t1/2 was 18.7 h. IC50 values of 24 h and 48 h were 18.5 and 9.8 μg/mL, respectively.Preparation and characterization of CMCS@MNPs/CDDP: Magnetic nanoparticles were successfully embedded carboxymethylated chitosan and cisplatin. Distribution particle size was 400 nm, volume average particle diameter were 37 and 396 nm. Ms was 70.4 emu/g. The wt of magnetic particles was 74.9 %, loading 49.70±0.12 % drug. When p H=7.4, cisplatin half-life t1/2 of sustainly drug releaseing was 22.4 h. IC50 values of 24 h and 48 h were 29.5 and 10.6 μg/mL, respectively.Preparation and Characterization of SiO2@MNPs-COOH-CDDP: The distribution particle size was about 200 nm, dynamics volume average particle diameters were 58 and 220 nm. Magnetic nanoparticles has been successfully embedded in silica, and derivatized with carboxyl and grafted with cisplatin. Ms was 26.3 emu/g. The wt of magnetic particles was 27.9 %, loading 46.15±3.47 % drug. When p H =7.4, cisplatin half- life t1/2 of sustainly drug releaseing was 11.3 h. IC50 of 24 h and 48 h were 21.4 μg/mL and 10.2 μg/mL, respectively.In summary, three kinds of particles were successfully prepared and characterized by varied methods, and researches of drug functions illustrated that all the composite particles possessed their drug-loading and therapeutic capabilities.更多还原