Abstract
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.