Chan Park Seok, Kim Min Jung, Choi Kyoungju, Kim Jooyoun, Choi Seong-O
Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University Manhattan KS USA
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University Manhattan KS USA.
RSC Adv. 2018 Sep 19;8(57):32470-32480. doi: 10.1039/c8ra05485a. eCollection 2018 Sep 18.
Developing a facile means of controlling drug release is of utmost interest in drug delivery systems. In this study, core-shell structured nanofibers containing a water-soluble porogen were fabricated solution blow spinning, to be used as drug-loaded bioactive tissue scaffolds. Hydrophilic polyvinylpyrrolidone (PVP) and hydrophobic poly(ε-caprolactone) (PCL) were chosen to produce the core and the shell compartments of the fiber, respectively. In the core, a hydrophilic sulforhodamine B (SRB) dye was loaded as a model drug. In the PCL shell, two kinds of PVP with different molecular weights (40 kDa and 1300 kDa) were added, and the influence of PVP leaching on the SRB release and cell growth was investigated. The monolithic PCL-shelled fibers displayed a sustained SRB release with a weak burst effect. The addition of PVP in the shell induced a phase separation, forming microscale PVP domains. The PVP domain, acting as a porogen, was leached out in the medium and, as a result, the burst release of SRB was promoted. This burst effect was more prominent with the lower molecular weight PVP. The biocompatibility of the core-shell fibers was evaluated with human epidermal keratinocytes (HEK) by a cell viability assay and microscopic observation of cell proliferation. The HEK cells on fibers with a PVP/PCL composite shell formed self-assembled spherical clusters, displaying higher cell viability and proliferation than those on the monolithic PCL-shelled fibers that induced HEK cell growth in two-dimensional monolayers. The results demonstrate that the presence of hydrophilic porogens on tissue scaffolds can accelerate drug release and enhance cell proliferation by increasing surface wettability, roughness and porosity. The findings of this study provide a basic insight into the construction of bioactive three-dimensional tissue scaffolds.
开发一种简便的药物释放控制方法在药物递送系统中至关重要。在本研究中,通过溶液吹纺制备了含有水溶性致孔剂的核壳结构纳米纤维,用作载药生物活性组织支架。分别选择亲水性聚乙烯吡咯烷酮(PVP)和疏水性聚(ε-己内酯)(PCL)来制备纤维的核层和壳层。在核层中,载入亲水性磺基罗丹明B(SRB)染料作为模型药物。在PCL壳层中,添加了两种不同分子量(40 kDa和1300 kDa)的PVP,并研究了PVP浸出对SRB释放和细胞生长的影响。整体PCL壳层纤维显示出SRB的持续释放且有较弱的突释效应。壳层中添加PVP会引起相分离,形成微米级的PVP区域。作为致孔剂的PVP区域在培养基中被浸出,结果促进了SRB的突释。分子量较低的PVP这种突释效应更显著。通过细胞活力测定和细胞增殖的显微镜观察,用人表皮角质形成细胞(HEK)评估了核壳纤维的生物相容性。具有PVP/PCL复合壳层的纤维上的HEK细胞形成了自组装球形簇,与在诱导HEK细胞在二维单层生长的整体PCL壳层纤维上的细胞相比,显示出更高的细胞活力和增殖能力。结果表明,组织支架上亲水性致孔剂的存在可通过增加表面润湿性、粗糙度和孔隙率来加速药物释放并增强细胞增殖。本研究结果为生物活性三维组织支架的构建提供了基本见解。