Background: Although electrohydrodynamic atomization (EHDA) consistently provides drug-encapsulation efficiencies (DEE) far above those of conventional bottom-up nanotechnologies, the question of how to systematically push that efficiency even higher remains largely unexplored. Methods: This study introduces a modified triaxial electrospinning protocol tailored to the application and benchmarks it against two conventional techniques: single-fluid blending and coaxial electrospinning. Ethylcellulose (EC) served as the polymeric matrix, while curcumin (Cur) was chosen as the model drug. In the triaxial setup, an electrospinnable, drug-free EC solution was introduced as an intermediate sheath to act as a molecular barrier, preventing Cur diffusion from the core fluid. Ethanol alone was used as the outermost fluid to guarantee a stable and continuous jet. Results: This strategy provided a DEE value of 98.74 ± 6.45%, significantly higher than the 93.74 ± 5.39% achieved by coaxial electrospinning and the 88.63 ± 7.36% obtained with simple blending. Sustained-release testing revealed the same rank order: triaxial fibers released Cur the most slowly and exhibited the smallest initial burst release effect, followed by coaxial and then blended fibers. Mechanistic models for both fiber production and drug release are proposed to clarify how the tri-layer core–shell structure translates into superior performance. Conclusions: The modified triaxial electrospinning was able to open a new practical route to produce core-sheath nanofibers. These nanofibers could provide a higher DEE and a better sustained drug release profile than those from the coaxial and blending processes.

To overcome the limitations of traditional motion sickness medications—slow onset of action, short duration of efficacy, and poor patient compliance—this study employed coaxial electrospinning technology. Poly(lactic acid) (PLA) and polyvinylpyrrolidone K90 (PVP K90) were used as composite carrier materials. The sheath layer is composed of highly hydrophilic PVP K90, loaded with the antihistamine diphenhydramine (DPH). The core layer, composed of biodegradable PLA with excellent sustained-release properties, carries the anticholinergic drug scopolamine hydrobromide (SH). This core–sheath nanostructured nanofiber sublingual film delivers dual anti-motion sickness drugs. A series of characterization tests revealed that the sublingual membrane exhibits a linear morphology with a distinct core–shell nanostructure. The drugs DPH and SH are distributed in an amorphous state within the sheath and core layers, respectively. Wetting performance tests indicate that the membrane’s wettability falls between those of monofilament membranes. In vitro drug release experiments revealed that DPH exhibited a “rapid onset + sustained release” biphasic profile, with cumulative release reaching 60% within 2 h and approaching complete release by 10 h, primarily via Fickian diffusion (n = 0.30). SH exhibited prolonged sustained release, approaching complete release at 12 h via non-Fickian diffusion (n = 0.55). Cytotoxicity and vital/necrotic staining experiments mutually corroborated that cell viability remained above 80%, further validating the safety and efficacy of PLA/PVP as a combined drug delivery carrier. This study provides a novel delivery system for motion sickness treatment, offering significant theoretical value and broad clinical application prospects.

Background: Simultaneous controlled release of multiple therapeutics from a single dosage form is a major frontier in modern pharmaceutics and a key strategy for modernizing traditional Chinese medicine. Methods: Using finasteride (FIN) and a Jing-Zhu hybrid Tibetan (JZ) herbal medicine as model agents for prostatitis therapy, we developed a modified tri-fluid electrospinning process to fabricate drug-co-loaded Janus medicated nanofibers. Soluble polyvinylpyrrolidone (PVP) and insoluble ethylcellulose (EC) served as carrier matrices for the dual faces of the Janus architecture, encapsulating JZ herbal medicine and FIN, respectively. A custom-designed spinneret—comprising two parallel stainless steel tubes nested within a plastic sheath—was engineered to enable side-by-side fiber formation. Results: Scanning and transmission electron microscopy confirmed linear morphologies with a definitive side-by-side Janus structure. X-ray diffraction and Fourier Transform Infrared Spectroscopy revealed that all active ingredients were dispersed in an amorphous state, reflecting polymer–drug compatibility. Encapsulation efficiencies reached 96.34 ± 0.47% for FIN and 94.15 ± 0.48% for JZ herbal medicine. A newly devised water-droplet assay demonstrated that almost all the nanofibers exhibited the intended side-by-side configuration, as evidenced by the rapid dissolution of the PVP side. In vitro release studies showed an initial pulsatile burst of JZ herbal medicine followed by a sustained FIN release profile, as suggested by the single-drug-loaded Janus nanofibrous controls. Conclusions: The present Janus nanostructure system, fabricated via a facile co-shell solvent electrospinning process, has the potential to enable the concurrent yet asynchronous delivery of FIN and JZ herbal components within a single nano-dosage form. This conceptual advance expands the toolkit for designing combination nanomedicines, allowing independent modulation of release kinetics for individual drugs to maximize prospective joint efficacy.

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.