Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Center for Biopharmaceuticals and Biobarriers in Drug Delivery, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Int J Mol Sci. 2022 Jan 27;23(3):1458. doi: 10.3390/ijms23031458.
The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber-film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
舌下黏膜是药物输送的一个有吸引力的途径，尽管它受到持续不断的唾液流动的挑战，这会导致药物通过吞咽而损失。药物通过舌下黏膜吸收可以避免暴露在胃肠道腔的恶劣环境中，这对低物理化学稳定性的药物如治疗性肽非常有益。在这项研究中，开发了一种双层混合药物输送系统，用于治疗性肽去氨加压素的舌下给药。它由载肽的粘膜粘附性静电纺丝壳聚糖/聚氧化乙烯基纳米纤维（平均直径为 183 ± 20nm）和一种排斥唾液的背衬膜组成，以促进向黏膜的单向释放。去氨加压素从基于纳米纤维的混合系统中以单向方式释放（约 80%的负载肽在 45 分钟内释放）。重要的是，纳米纤维-薄膜混合系统保护了肽免受冲洗，这在猪舌下黏膜组织的体外流动保留模型中得到了证明。在代表唾液流量的流速下暴露 15 分钟后，约 90%的负载去氨加压素保留在猪舌下黏膜的表面。
