Fatty acid and quaternary ammonium modified chitosan nanoparticles for insulin delivery.
Fatty acid and quaternary ammonium modified chitosan nanoparticles for insulin delivery.
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DOI：
10.1016/j.colsurfb.2018.05.063
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Hongxiang Li;Zhe Zhang;Xiaoyan Bao;Guangrui Xu;Ping Yao
中科院分区：
文献类型：
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作者：
Hongxiang Li;Zhe Zhang;Xiaoyan Bao;Guangrui Xu;Ping Yao
肝脏是胰岛素发挥生理功能的主要器官。本研究将月桂酸和油酸分别偶联到季铵化壳聚糖上，以脂肪酸修饰的壳聚糖衍生物为载体，将负载的胰岛素输送到肝脏。利用胰岛素与壳聚糖衍生物之间的静电和疏水相互作用制备了尺寸约为280 nm的纳米颗粒。壳聚糖衍生物的胰岛素负载效率和胰岛素负载量均大于98%。纳米颗粒的表面疏水性随壳聚糖衍生物的脂肪酸取代度和脂肪酸疏水性的增加而增加。表面疏水性高的纳米颗粒表现出更高的肝细胞吸收、更多的肝脏蓄积和更好的抗糖尿病效果。与胰岛素治疗组相比，月桂酸和油酸纳米颗粒治疗组皮下注射糖尿病小鼠后的相对药理学有效度分别为233%和311%。本研究表明，由脂肪酸修饰聚合物制备的纳米颗粒是一种有效的肝脏靶向胰岛素递送系统。
Liver is the major organ where insulin performs its physiological function. In this study, lauric acid and oleic acid were respectively conjugated to quaternized chitosan, and the fatty acid modified chitosan derivatives were used as the carriers to deliver the loaded insulin to liver. The nanoparticles with sizes of about 280 nm were fabricatedviathe electrostatic and hydrophobic interactions between insulin and the chitosan derivative. Both of insulin loading efficiency and loading capacity of the chitosan derivatives were higher than 98%. The surface hydrophobicity of the nanoparticles increased with the increases of fatty acid hydrophobicity and also fatty acid substitution degree of the chitosan derivative. The nanoparticles with higher surface hydrophobicity displayed higher hepatocyte absorption, more accumulation in the liver and better antidiabetic efficacy. Compared with free insulin treatment group, the relative pharmacological availabilities were 233% and 311% for the groups treated with the nanoparticles having lauric acid and oleic acid, respectively, after subcutaneous injection into diabetic mice. This study demonstrates that the nanoparticles fabricated from fatty acid modified polymer are an effective liver-targeted delivery system of insulin.