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.