Wang Xiaodan, Gu Xiangqin, Wang Huimin, Sun Yujiao, Wu Haiyang, Mao Shirui
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Eur J Pharm Sci. 2017 Jan 1;96:255-262. doi: 10.1016/j.ejps.2016.09.036. Epub 2016 Sep 28.
Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6-260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.
近年来，具有多种功能的聚合物材料作为药物递送系统设计的载体受到了广泛关注。在本研究中，通过对透明质酸进行羟基修饰，合成了一系列多功能药物递送载体，即透明质酸（HA）-甘草次酸（GA）琥珀酸酯（HSG）共聚物。结果表明，HSG纳米颗粒呈亚球形，粒径在152.6 - 260.7nm范围内，具体取决于GA接枝率。HSG纳米颗粒具有良好的短期稳定性和稀释稳定性。MTT法检测表明，所有共聚物均无明显细胞毒性。体内成像分析表明，HSG纳米颗粒具有优异的肝脏靶向效率，且肝脏靶向能力与GA接枝率有关。负载DiR（一种亲脂性近红外荧光花菁染料）的HSG - 6、HSG - 12和HSG - 20纳米颗粒在肝脏中的蓄积量分别比游离DiR高1.8倍、2.1倍和2.9倍。GA在HA上的结合位点可能会影响肝脏靶向效率。这些结果表明，基于HSG共聚物的纳米颗粒是潜在的可提高肝脏靶向性的药物载体。
