An Electrospun Core-Sheath/Janus-Integrated Hierarchical Structure for Asynchronous Mucosal Drug Delivery

Background: It is highly desirable to address the dual therapeutic needs of quickly alleviating clinical symptoms and providing long-lasting effects for motion sickness, as well as to overcome limitations of traditional electrospinning methods-such as easy drug mixing, poor zoning accuracy, and inadequate controlled-release capabilities. Methods: This study developed a self-developed trifluid electrospinning device. This device was used to create a dual-drug loaded nanofiber membrane containing diphenhydramine (DP) and scopolamine hydrobromide (SH), featuring a zoned structure composed of a polyvinylpyrrolidone (PVP) crescent side chamber, a round polylactic acid (PLA) sheath chamber, and a round PLA core chamber. Results: The results demonstrated that the fibers maintained an intact structure with distinct interfaces, allowing precise zoned loading of the two drugs, which were present in an amorphous dispersed state, indicating good compatibility and structural stability. The nanofiber membrane showed moderate mechanical strength and excellent hydrophilicity, making it suitable for oral mucosal drug delivery. Asynchronous drug delivery, featuring a rapid release of DP (53% at 1 h) and a sustained release of SH (85% at 12 h with no noticeable burst phenomenon), was demonstrated using two types of hierarchically structured nanofibers, each loaded with a single drug to facilitate measurement. The release mechanisms were disclosed for DP and SH from the tri-chamber hierarchical nanofibers. Cell studies confirmed its good biocompatibility. Conclusions: This work offers new insights and experimental evidence for developing an effective synergistic oral delivery system for motion sickness and advancing multifunctional nanocarrier drug delivery platforms.