透皮芦荟苦素纳米粒的制备及其对酪氨酸酶活性的抑制作用

Synthesis of transdermal aloesin loaded zinc oxide nanoparticles and its inhibitory effect on the activity of tyrosinase

采用溶胶-凝胶法制备氧化锌量子点(ZnO QDs),表面用3-氨丙基三乙氧基硅烷(APTES)改性,制备氨基化的ZnO QDs。同时,利用N,N′-羰基二咪唑(CDI)活化芦荟苦素(Alo),与氨基化的ZnO QDs反应,将Alo共价连接在ZnO QDs表面,获得芦荟苦素纳米粒(Alo NPs)。采用透射电子显微镜(TEM)、动态光散射仪(DLS)、傅里叶变换红外光谱仪(FTIR)和热重分析仪(TGA)对Alo NPs的形貌、粒径、结构进行了表征。测试表明,ZnO QDs呈类圆形,由于Alo的连接,原本粒径分布在4 nm左右的粒子粒径增加至8 nm左右。TG结果显示Alo NPs中,ZnO QDs和Alo的质量分数分别为39.27%、35.14%。透皮渗透实验结果表明Alo NPs能显著提高Alo的透皮效率。体外释药行为显示,Alo-NPs在酸性条件下(pH=5.0)2 h即能释放87.63%±0.46%的Alo,而在pH=7.4的介质中,2 h内的累积释放率只有1.45%±0.21%。Alo-NPs对酪氨酸酶活性抑制率呈浓度依赖型,当ZnO QDs的当量溶度为12.5μg/mL时,抑制率可高达40.32%±1.57%。这些结果说明Alo NPs作为外用酪氨酸酶活性抑制剂具有潜在的应用价值。

Zinc oxide quantum dots(ZnO QDs)were synthesized by gel-sol method and employed as the transdermal aloesin(Alo)carriers.ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane(APTES).Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs,which were characterized by transmission electron microscope(TEM),dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FTIR)and thermal gravimetric analyzer(TGA).TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution,of which was around 4 nm.The size of Alo NPs increased to around 8 nm due to the surface modification.The intense bands at around 3 400 cm–1 and 1 200 cm–1 in the FTIR spectrum of Alo NPs from the vibration of-OH indicated the linkage of Alo on the surface of ZnO QDs.The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27%and 35.14%,respectively.The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin,which manifested the improvement of the penetration for Alo delivered by ZnO QDs.The pH-controlled drug release behavior in vitro was investigated.At pH 7.4,only a small amount of Alo(1.45%±0.21%)had been released after 2 h.In contrast,as incubation at pH 5.0 of which pH was similar to endosomal environment,Alo was released very fast(87.63%±0.46%in 2 h)from Alo NPs,confirming that Alo NPs could response to the pH and realize the intracellular drug release.The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner.When the concentration of Alo NPs was 12.5μg/mL,the inhibition rate was up to 40.32%±1.57%.All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.