Influence of drug distributions within electrospun architectures on icariin sustained release from polycaprolactone nanofibers.

The fabrication architecture of electrospun drug-loaded nanofibers is pivotal in regulating drug distribution and release kinetics. However, systematic comparisons of electrospinning-based drug-loading strategies under identical experimental conditions remain scarce. In this study, four electrospinning architectures, including blend electrospinning, electrospraying, coaxial (core-shell), and triaxial electrospinning, were compared to elucidate how structural configuration influences the morphology, mechanical behavior, and release kinetics of icariin -loaded polycaprolactone nanofibers. Electrospun membranes were fabricated using the same polymer matrix, nominal drug loading, and processing conditions to ensure a direct comparison between architectures. Morphological characterization showed that electrosprayed fibers had rougher surfaces and larger average fiber diameters, whereas Core-sheath and tri-chamber fibers displayed smoother, more uniform morphologies. In a single release study per architecture, multilayer architectures showed a lower initial burst release, with tri-chamber nanofibers exhibiting the lowest initial burst (approximately 3.7%) and a sustained cumulative release of approximately 25% over 168 h. Kinetic modeling showed that the tri-chamber l architecture had the strongest agreement with the Higuchi model (R2 = 0.9898) and the highest zero-order correlation (R2 = 0.8747), indicating diffusion-controlled release from a multilayer reservoir structure. In contrast, the electrospinning-electrospraying blend showed faster release profiles dominated by surface-associated drug diffusion. These findings suggest that electrospinning architecture is a key determinant of drug encapsulation stability and release behavior, a trend that requires confirmation with replicate batches. The present work establishes a rational framework for selecting electrospinning strategies to engineer sustained-release nanofibrous drug-delivery systems for regenerative medicine and localized therapeutic applications.