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目的制备粒径相对可控的壳聚糖纳米粒,探索其在药物缓释体系中的应用。方法以多聚磷酸钠为离子诱导剂、戊二醛为化学交联剂,通过离子诱导结合化学交联法,制备壳聚糖纳米粒;在1-乙基-(3-二甲氨基丙基)碳二亚胺盐酸盐(EDC)作用下,分别进行丝裂霉素载药以及聚乙二醇(PEG),叶酸修饰;另外,对载药纳米粒子进行不同pH条件下的体外释药实验;对PEG,叶酸修饰的壳聚糖纳米粒罗丹明B荧光标记后,进行激光共聚焦以及活体成像实验。结果离子诱导交联法可以获得粒径范围在200~500 nm的壳聚糖纳米粒;丝裂霉素载药量可以达到25%,包封率为50%,体外释药呈现突释和缓释双相特征,并且随着pH的升高释药明显加快;未经修饰的、叶酸修饰的以及PEG和叶酸修饰的纳米粒都能有效的进入Hela细胞,而单独PEG修饰的却很少进入细胞内;叶酸修饰的纳米粒有明显的靶向作用,PEG修饰的纳米粒可以明显延长实验裸鼠血液中循环时间。结论采用离子诱导结合化学交联法可以获得粒径可控、稳定、适合于主动靶向给药的壳聚糖纳米粒。
Objective To prepare chitosan nanoparticles with relatively controlled particle size and to explore its application in drug delivery system. Methods Chitosan nanoparticles were prepared by sodium polyphosphate as an ion-inducing agent and glutaraldehyde as a chemical cross-linking agent by ion-induced and chemical cross-linking method. In the presence of 1-ethyl- (3-dimethylaminopropyl ) Carbodiimide hydrochloride (EDC) under the action of respectively, mitomycin drug delivery and polyethylene glycol (PEG), folic acid modification; In addition, drug-loaded nanoparticles in different pH conditions in vitro release Experiments; PEG, folic acid modified chitosan nanoparticles rhodamine B fluorescent labeling, laser confocal and in vivo imaging experiments. Results The ion-induced cross-linking method could obtain chitosan nanoparticles with particle size in the range of 200-500 nm. The drug loading of mitomycin could reach 25% and the entrapment efficiency was 50% Release biphasic characteristics, and with the pH increased drug release was significantly accelerated; unmodified, folic acid modified and PEG and folic acid modified nanoparticles can effectively enter the Hela cells, while the PEG-modified but rarely entered Intracellular; folate-modified nanoparticles have obvious targeting effect, PEG-modified nanoparticles can significantly extend the experimental nude mice blood circulation time. Conclusion Ion-induced and chemical cross-linking can be used to obtain chitosan nanoparticles with controlled particle size and stability.