透明质酸修饰的pH敏感载多柔比星纳米粒的制备及初步评价

The Preparation and Pre-Evaluation of Hyaluronic Acid Modified pH-Sensitive Nanoparticles with Doxorubicin Loaded

研究了一种透明质酸(HA)修饰的pH敏感载多柔比星(DOX)纳米粒(HA/PEI-DOX,HPD)的制备过程,并对其理化性质和体外释药性质进行初步评价。首先合成pH敏感载多柔比星聚合物材料PEI-DOX,随后与HA通过静电相互作用自组装形成HPD。通过对其进行理化性质初步评价,确定的最优处方纳米粒平均粒径为(101.6±2.9)nm,Zeta电位为(-24.4±0.89)mV。透射电镜观察其形态圆整。体外释放实验结果显示HPD具有一定pH敏感性。

In this study,a kind of hyaluronic acid（HA） modified pH-sensitive nanoparticles with doxorubicin（DOX） loaded（HA/PEI-DOX,HPD） was built.In order to confirm the optimal formulation of HPD,the physical and chemical properties of HPD were evaluated.Firstly,pH-sensitive hydrazone linked cationic conjugate poly（ethyleneimine）-C6-succinimidyl 6-hydrazinonicotinate acetone hydrazone-DOX（PEI-DOX） was synthesized.Secondly,blank nanoparticles HP was built by the crosslink of PEI and HA,and the physicochemical properties of HP were preliminarily evaluated.Thirdly HPD was built by the crosslink of PEI-DOX and HA,and the physicochemical properties of HPD were preliminarily evaluated.Fourthly,in vitro pH-sensitive drug release test of HPD was conducted.As a result,the successful synthesis of PEI-DOX was confirmed by ~1H nuclear magnetic resonance and infrared spectroscopy in our previous work.At the optimal formulation of HP,the concentration of HA was 450 μg/m L,the concentration of PEI was 125 μg/m L,and the weight ratio of HA to PEI was 18∶ 5.The average size of optimal formulation was（83.57 ± 4.2） nm,PDI was0.127 ± 0.019 and Zeta potential was（-25.8 ± 0.48） m V.As shown in TEM picture,HP displayed a spherical morphology.At the optimal formulation of HPD,the concentration of HA was 450 μg/m L,the concentration of PEI-DOX was 150 μg/m L,and the weight ratio of HA to PEI-DOX was 18∶ 6.The average size of the optimal formulation of HPD was（101.6 ± 2.9） nm,Zeta potential was（-24.4 ± 0.89） mV.As shown in TEM picture,HPD displayed a spherical morphology.In the in vitro pH-sensitive drug release test,cumulative release percentage of DOX at pH 5.0[（49.2 ± 2.53） %,48 h] was more than that at pH 7.4[（12.0 ± 2.37） %,48 h],（P 0.005）.In conclusion,the HA modified pH-sensitive nanoparticles with DOX loaded（HPD） were built,and pH-sensitive DOX release from HPD was confirmed in vitro.