A Process Optimization and Release Modeling of Coaxial Electrospun Aligned Core‐Shell Poly (Ethylene Oxide‐Poly( <scp>l</scp> ‐Lactide‐Co‐Glycolide)) (PEO‐PLGA) Nanofibers Encapsulating Nerve Growth Factor

Recent advances in neural regeneration have demonstrated the importance of incorporating proteins into polymeric capsules to provide both topographical and biochemical cues to cells. Coaxial electrospinning has emerged as a versatile technique for embedding delicate bioactive agents within core-shell nanofibers, enabling controlled and sustained drug release. In this study, we employed a design-of-experiment approach to systematically investigate how controllable parameters in coaxial electrospinning influence the diameter and size distribution of aligned poly (ethylene oxide-poly(l-lactide-co-glycolide) nanofibers loaded with nerve growth factor (NGF). Employing a Box-Behnken Design, we identified the optimal parameter levels to minimize the response variables and conducted a regression analysis. The results indicated that optimal core-shell nanofibers, with a minimized fiber diameter of 323 nm and a fiber size distribution of 2.37%, were achieved by setting the inner flow rate to 0.33 mL h^-1, the outer flow rate to 2 mL h^-1, the collector speed to 500 rpm, the applied voltage to 17 kV, and the distance between the coaxial needle and the collector to 10 cm. Statistical analysis revealed that the inner flow rate, collector distance, and voltage significantly impacted nanofiber diameter, while collector speed was a key factor for fiber size distribution. Diagnostic plots for model evaluation showed high predictive accuracy for fiber diameter (R²=0.8) but limited accuracy for fiber size distribution (R² =0.5). Using these optimized parameters, we characterized the NGF release profile from the fibers, observing an initial burst release (~81% within 8 hours), followed by sustained, near zero-order release (~13% over two weeks). The release kinetics were well-fitted to a Michaelis-Menten model, suggesting that PEO core dissolution followed by PLGA degradation governs the biphasic release behavior. This work offers a more efficient and sustainable approach to fabricating NGF-loaded, highly aligned core-shell nanofibers with a minimal diameter and narrow size distribution.