CIESC Journal ›› 2015, Vol. 66 ›› Issue (4): 1565-1576.DOI: 10.11949/j.issn.0438-1157.20141349

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Preparation and characterization of chitosan nanoparticles/PLLA-PEG-PLLA composite microparticles by supercritical fluid technology

CHEN Aizheng1,2, KANG Yongqiang1, WANG Shibin1,2, TANG Na1, ZHAO Hui1   

  1. 1. School of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian, China;
    2. Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, Fujian, China
  • Received:2014-09-04 Revised:2015-01-04 Online:2015-04-05 Published:2015-04-05
  • Supported by:

    supported by the National Natural Science Foundation of China (31470927, 31170939, 51103049).

超临界流体技术构建壳聚糖纳米粒/PLLA-PEG-PLLA 复合微粒及其表征

陈爱政1,2, 康永强1, 王士斌1,2, 唐娜1, 赵晖1   

  1. 1. 华侨大学化工学院, 福建 厦门 361021;
    2. 华侨大学生物材料与组织工程研究所, 福建 厦门 361021
  • 通讯作者: 陈爱政
  • 作者简介:陈爱政(1978-),男,博士,研究员。
  • 基金资助:

    国家自然科学基金项目(31470927,31170939,51103049)。

Abstract:

The carriers with core-shell structure have been widely used in the field of co-loading gene and drug. In this study, chitosan (CS) nanoparticles (CS NPs)/poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) triblock copolymer (PLLA-PEG-PLLA) composite microparticles (MPs) with core-shell structure were prepared by the combination of ion gelation and suspension-enhanced dispersion by supercritical fluids (SpEDS). The conditions for preparation of CS NPs and MPs were investigated and optimized, and the physicochemical properties and cytotoxicity of MPs were studied. The optimized condition for CS NPs were chitosan solution concentration of 2 mg·ml-1, chitosan solution pH of 5.0, and tripolyphosphate (TPP) solution concentration of 1 mg·ml-1. The ratio of solvent/non-solvent was the significant factor affecting sizes of MPs, and the optimized conditions for MPs were oil concentration of 5 mg·ml-1, W/O ratio of 0.75:10.00, solution flow rate of 2 ml·min-1 and solvent/non-solvent of 0.5:1.0. The MPs from optimized conditions had a size of 323.7 nm and the CS NPs were encapsulated in MPs, as observed by TEM. The results of experiments about physicochemical properties revealed that a reaction happened between CS and TPP. Little change occurred in the functional groups of materials used in the two processes, while the crystal forms of PLLA-PEG-PLLA in MPs were more uniform. The relative growth rates of Bcap-37 cells co-cultured with MPs with different concentrations of 0.25, 0.50 and 1.00 mg·ml-1 for 3 d were 105.3%, 101.9% and 100.9%, respectively. The above results demonstrated that the MPs with good biocompatibility could be used in the field of co-delivery for gene and antitumor drug to evaluate the antitumor effect and would achieve a good synergistic effect in the treatment of cancer.

Key words: supercritical fluid, co-loaded carrier, PLLA-PEG-PLLA, chitosan, composites, granulation

摘要:

利用离子凝胶法和超临界强制分散悬浮液(SpEDS)技术制备具有核壳型结构的壳聚糖纳米粒(CS NPs)/聚乳酸-聚乙二醇-聚乳酸三嵌段共聚物(PLLA-PEG-PLLA)复合微粒,考察和优化了壳聚糖纳米粒和复合微粒的制备条件,并对二者的理化性质和细胞毒性进行研究。结果表明,壳聚糖纳米粒的制备优化条件为壳聚糖浓度2 mg·ml-1、pH 5.0、三聚磷酸钠浓度1 mg·ml-1。溶剂/非溶剂比为复合微粒粒径的显著影响因素,复合微粒的制备优化条件为油相浓度5 mg·ml-1、水油比0.75:10.00、溶液流速2 ml·min-1、溶剂/非溶剂比0.5:1.0。优化条件制得的复合微粒粒径为323.7 nm,透射电镜(TEM)显示其具有核壳型结构。理化表征结果显示壳聚糖与三聚磷酸钠发生作用,但制备工艺前后材料官能团未发生明显变化,而且复合微粒中PLLA-PEG-PLLA晶型更加均匀;不同浓度组的CS NPs/PLLA-PEG-PLLA复合微粒(0.25、0.50和1.00 mg·ml-1)的细胞相对增殖率分别为105.3%、101.9%和100.9%,细胞毒性分级为0级,表明具有核壳结构的CS NPs/PLLA-PEG-PLLA复合微粒生物相容性良好,有望进一步应用于共载基因和抗癌药物的抗癌活性研究。

关键词: 超临界流体, 共载载体, 聚乳酸-聚乙二醇-聚乳酸三嵌段共聚物, 壳聚糖, 复合材料, 造粒

CLC Number: