Wang Qiuyue, Li Mingming, Sun Xinxing, Chen Naiying, Yao Sicheng, Feng Xun, Chen Yang
Department of Pharmaceutics, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
Department of Sanitary Chemistry, School of Public Health, Shenyang Medical College, No. 146 Yellow River North Street, Shenyang, 110034, China.
J Mater Chem B. 2023 Feb 22;11(8):1782-1797. doi: 10.1039/d2tb02361j.
Metal-organic frameworks (MOFs) are highly promising as a novel class of drug delivery carriers; however, there are few reports about their application in nanoparticle-based formulations for dermal administration. In this work, we developed a novel kind of nanoparticular system based on zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA) modification for improving the dermal delivery of 5-fluorouracil (5-FU). The structures and properties of the prepared nanoparticles were characterized using a variety of analytical methods. Their delivery performance in the skin was investigated using Franz cells, and the underlying mechanisms were studied confocal laser scanning microscopy (CLSM) and hematoxylin-eosin (HE) experiments which were employed to probe the penetration pathway and the interaction between nanoparticles and the skin. The results revealed that both 5-FU@ZIF-8 and ZIF-8@5-FU@PDA had an enhancement effect on the deposition of 5-FU in the skin, and the surface coating of PDA could further reduce drug permeation across the skin, especially in the case of impaired skin, in comparison with the drug solution. The CLSM study using rhodamine 6G as the fluorescent probe to mimic 5-FU indicated that ZIF-8 and ZIF-8@PDA could deliver their payloads into the skin two pathways, , intercellular and follicular ones, and the follicular route was shown to be particularly important for ZIF-8@PDA, in which the drug and carrier were co-delivered into the skin as an intact particle. This study provides evidence for using ZIF-8 and PDA modification for skin-specific drug delivery and offers an effective avenue to develop novel nanoplatforms for dermal application to treat skin diseases.
金属有机框架（MOFs）作为一类新型药物递送载体具有很高的应用前景；然而，关于其在基于纳米颗粒的皮肤给药制剂中的应用报道却很少。在本研究中，我们开发了一种基于沸石咪唑酯骨架-8（ZIF-8）和聚多巴胺（PDA）修饰的新型纳米颗粒系统，以改善5-氟尿嘧啶（5-FU）的皮肤递送效果。使用多种分析方法对制备的纳米颗粒的结构和性质进行了表征。使用Franz扩散池研究了它们在皮肤中的递送性能，并通过共聚焦激光扫描显微镜（CLSM）和苏木精-伊红（HE）实验研究了其潜在机制，这些实验用于探究渗透途径以及纳米颗粒与皮肤之间的相互作用。结果表明，5-FU@ZIF-8和ZIF-8@5-FU@PDA对5-FU在皮肤中的沉积均有增强作用，与药物溶液相比，PDA的表面包覆可进一步减少药物透过皮肤，尤其是在皮肤受损的情况下。使用罗丹明6G作为荧光探针模拟5-FU的CLSM研究表明，ZIF-8和ZIF-8@PDA可通过两条途径将其有效载荷递送至皮肤，即细胞间途径和毛囊途径，并且毛囊途径对ZIF-8@PDA尤为重要，其中药物和载体作为完整颗粒共同递送至皮肤。本研究为使用ZIF-8和PDA修饰进行皮肤特异性药物递送提供了证据，并为开发用于皮肤疾病治疗的新型皮肤应用纳米平台提供了有效途径。
