Sun Yuhao, Zhou Jianfeng, Zhang Zhiyuan, Yu Deng-Guang, Bligh Sim Wan Annie
Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China.
Int J Pharm. 2024 Jun 10;658:124180. doi: 10.1016/j.ijpharm.2024.124180. Epub 2024 May 4.
During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.
在过去几十年中,纳米结构对新型纳米药物递送系统的发展产生了越来越大的影响,其中双腔Janus纳米结构是一种常见的结构。在本研究中,开发了一种新型三通道喷丝头,其中两个平行的金属毛细管以核壳方式嵌套在另一个金属毛细管中。以溶剂混合物作为壳层工作流体进行三流体静电纺丝,以确保形成完整的Janus纳米结构。扫描电子显微镜结果表明所得纳米纤维具有线性形态,并且在其内部有两个不同的隔室,这在横截面图像中得到了体现。傅里叶变换红外光谱和X射线衍射图谱证实,负载的难溶性药物即淫羊藿苷,在Janus载药纳米纤维中呈无定形状态,这应归因于淫羊藿苷与两种可溶性聚合物基质即羟丙基甲基纤维素(HPMC)和聚乙烯吡咯烷酮(PVP)之间良好的二级相互作用。体外溶出试验表明,当淫羊藿苷封装在Janus纳米纤维中时,可以在5分钟内完全释放,这比原料药颗粒快11倍以上。此外,体外渗透试验表明,淫羊藿苷的渗透速率比药粉高16.2倍。这种改善归因于药物的快速溶解以及跨膜增强剂十二烷基硫酸钠从纳米纤维的PVP侧预释放。提出了微观形成、药物释放和渗透的机制。基于本研究中概述的方法,未来可以为难溶性药物开发许多基于Janus纳米结构的新型纳米药物递送系统。