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季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验

苑旺,  王美玲,  石岩,  崔黎丽

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文章导航 > 药学实践与服务  > 2015 >  33(4): 319-323
苑旺, 王美玲, 石岩, 崔黎丽. 季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验[J]. 药学实践与服务, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
引用本文: 苑旺, 王美玲, 石岩, 崔黎丽. 季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验[J]. 药学实践与服务, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
shu
YUAN Wang, WANG Meiling, SHI Yan, CUI Lili. Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
Citation: YUAN Wang, WANG Meiling, SHI Yan, CUI Lili. Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
shu

季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验

doi: 10.3969/j.issn.1006-0111.2015.04.008
  • 1.

    第二军医大学 药学院无机化学教研室, 上海 200433

  • 2.

    第二军医大学 基础部数理教研室, 上海 200433

  • 3.

    第二军医大学 海军医学系, 上海 200433

基金项目: 国家自然科学基金(No.51477175)

Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles

  • 1.

    Department of Inorganic Chemistry, School of Pharmacy; Second Military Medical University, Shanghai 200433, China

  • 2.

    Department of Physics and Mathematics, College of Basic Medical Sciences; Second Military Medical University, Shanghai 200433, China

  • 3.

    College of Naval Medicine, Second Military Medical University, Shanghai 200433, China

  • 摘要: 目的 采用正交设计试验优化载胰岛素季铵化壳聚糖纳米粒的处方工艺,并初步考察其降糖效果。 方法 用离子交联法制备载胰岛素的季铵化壳聚糖纳米粒,用正交试验确定其最佳处方工艺。用透射电子显微镜观察纳米粒的表面形态;用粒径/Zeta电位仪测定纳米粒的粒径和Zeta电位;用高效液相色谱(HPLC)法测定纳米粒的包封率、载药量及体外释放情况。对糖尿病大鼠皮下注射给药,对其药效学进行初步考察。 结果 制得的纳米粒呈球形,分布均匀;平均粒径(63.26±1.88) nm;Zeta电位(33.1±0.3) mV;包封率(37.92±2.11)%;载药量(5.42±0.3)%;24 h累计释放率63.83%。皮下注射给药8 h,糖尿病大鼠血糖较单纯注射胰岛素组下降平缓,且药效持久。 结论 优化后的载胰岛素的季铵化壳聚糖纳米粒形态较好、粒径较小,为研究胰岛素的新型给药途径奠定了基础。
    Abstract: Objective To prepare and optimize insulin-loaded N-trimethyl chitosan nanoparticles via orthogonal design, and preliminarily study the effects on blood glucose level. Methods The insulin-loaded N-trimethyl chitosan nanoparticles(INS-NPs) were prepared by ionic gelation, and the optimal proportion was obtained with orthogonal design. The nanoparticles were characterized by transmission electron microscopy and zeta/sizer nano analyzer. The entrapment efficiency of insulin-loaded nanoparticles and the in vitro releasing characteristics were studied by HPLC. A preliminary pharmacodynamic study of the insulin-loaded nanoparticles was also carried out. Results The INS-NPs exhibited narrow distribution. The mean diameter of INS-NPs was (63.26±1.88)nm, while the entrapment efficiency was (37.92±2.11)%. After 8 hours of subcutaneous injection of the INS-NPs, the blood glucose level in diabetic rats decreased to normal level and kept stable. Conclusion The optimized insulin-loaded nanoparticles had homogeneous spherical shape, small size, and could be a new approach of administration for insulin.
  • [1] Unwin N, Gan D, Whiting D. The IDF diabetes atlas: providing evidence, raising awareness and promoting action [J]. Diabetes Res Clin Pract, 2010, 87(1): 2-3.
    [2] 韩丽娜,尹丽芳,赵月芳,等.胰岛素/维生素B12-透明质酸纳米粒的制备及口服给药体内外性质的评价[J].中山大学学报,2012,33(5): 597-602.
    [3] 欧 歌,廖德华,张 凯,等.采用离子交联法制备壳聚糖胰岛素纳米粒的研究进展[J].中南药学,2013,11(2): 111-119.
    [4] Avadi MR, Sadeghi AM, Mohammadpour N, et al. Preparation and characterization of insulin nanoparticles using chitosan and arabic gum with ionic gelation method[J]. Nanomedicine, 2010, 6(1): 58-63.
    [5] 曹 姗,胡凯莉,刘 梅,等.多西紫杉醇口服磷脂纳米粒的制备与处方优化[J].中成药,2013, 35(9): 1896-1900.
  • [1] 王耀振, 徐灿, 吕顺莉, 田泾, 张东炜.  钾离子竞争性酸阻滞剂的药学特征研究进展 . 药学实践与服务, 2024, 42(7): 278-284. doi: 10.12206/j.issn.2097-2024.202306040
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  • 收稿日期:  2015-02-10
  • 修回日期:  2015-06-02

季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验

doi: 10.3969/j.issn.1006-0111.2015.04.008
  • 1. 第二军医大学 药学院无机化学教研室, 上海 200433
  • 2. 第二军医大学 基础部数理教研室, 上海 200433
  • 3. 第二军医大学 海军医学系, 上海 200433
    • 基金项目:  国家自然科学基金(No.51477175)
  • 收稿日期: 2015-02-10
  • 修回日期: 2015-06-02

摘要: 目的 采用正交设计试验优化载胰岛素季铵化壳聚糖纳米粒的处方工艺,并初步考察其降糖效果。 方法 用离子交联法制备载胰岛素的季铵化壳聚糖纳米粒,用正交试验确定其最佳处方工艺。用透射电子显微镜观察纳米粒的表面形态;用粒径/Zeta电位仪测定纳米粒的粒径和Zeta电位;用高效液相色谱(HPLC)法测定纳米粒的包封率、载药量及体外释放情况。对糖尿病大鼠皮下注射给药,对其药效学进行初步考察。 结果 制得的纳米粒呈球形,分布均匀;平均粒径(63.26±1.88) nm;Zeta电位(33.1±0.3) mV;包封率(37.92±2.11)%;载药量(5.42±0.3)%;24 h累计释放率63.83%。皮下注射给药8 h,糖尿病大鼠血糖较单纯注射胰岛素组下降平缓,且药效持久。 结论 优化后的载胰岛素的季铵化壳聚糖纳米粒形态较好、粒径较小,为研究胰岛素的新型给药途径奠定了基础。

English Abstract

苑旺, 王美玲, 石岩, 崔黎丽. 季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验[J]. 药学实践与服务, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
引用本文: 苑旺, 王美玲, 石岩, 崔黎丽. 季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验[J]. 药学实践与服务, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
shu
YUAN Wang, WANG Meiling, SHI Yan, CUI Lili. Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
Citation: YUAN Wang, WANG Meiling, SHI Yan, CUI Lili. Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 319-323. doi: 10.3969/j.issn.1006-0111.2015.04.008
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