Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Thessaloniki, Greece.
Laboratory of Biotechnology, Department of Biological Applications and Technologies, University of Ioannina, 45110 Ioannina, Greece.
Int J Pharm. 2024 Oct 25;664:124627. doi: 10.1016/j.ijpharm.2024.124627. Epub 2024 Aug 22.
3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.
通过半固态挤出技术制备了由 Carbopol 和 Eudragit 组成的 3D 打印剂型，将依诺肝素（Enox）和渗透增强剂 SNAC 组合在一个单一的步骤中，无需后续的后处理。使用流变学和傅里叶变换红外（FTIR）光谱对油墨进行了表征。通过核磁共振（NMR）和圆二色性（CD）分析评估了 Enox 在制备剂型中的稳定性。体外释放研究表明，Enox 以持续的方式释放，而体外实验则证明了 3D 打印剂型的粘膜粘附特性及其增强 Enox 跨肠道粘膜渗透的能力。细胞实验（CCK-8 实验）显示，与 3D 打印剂型孵育后，呈现剂量和时间依赖性的响应。SNAC 包封在 3D 打印剂型中证明了它们能够以可逆的方式增加跨细胞运输穿过 Caco-2 单层的大分子，这一点通过跨上皮电阻（TEER）测量得到了证实。
