生物医学工程学杂志

生物医学工程学杂志

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

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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)、纳米激光粒度仪(DLS)、傅氏转换红外线光谱分析仪(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 12.5 μg/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 12.5 μg/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.

关键词: 芦荟苦素; 氧化锌量子点; 酪氨酸酶抑制剂; 透皮运输; 控制释放

Key words: aloesin; zinc oxide quantum dots; tyrosinase inhibitor; transdermal delivery; controlled release

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