Polylactic acid (PLA) is a biodegradable polymer with high tensile strength, high stiffness, and biocompatibility, but its brittleness and hydrophobicity limit its applications. This study aims to address these limitations by blending PLA with polycaprolactone (PCL) to enhance flexibility and with polyethylene oxide (PEO) to improve hydrophilicity. Unlike conventional approaches where PEO serves as a plasticizer, this study investigated PEO as a major blend component. Electrospinning and solvent casting, which differ in their solvent evaporation rates, were employed to fabricate thin films of neat PLA and PLA blends to examine their influence on mechanical and surface properties. Polymer solutions were prepared using a dichloromethane (DCM)/dimethylformamide (DMF) mixture known to enhance the electrospinning process. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) were used to investigate crystallinity of polymers and their interactions, while scanning electron microscopy (SEM) and atomic force microscopy (AFM) provided insights into phase separation and fiber morphology. Uniaxial tensile testing and water contact angle measurements were conducted to evaluate mechanical properties and surface properties, respectively. The results showed that electrospun PLA films exhibited higher elongation at break and ultimate strength but lower Young’s modulus than solvent-cast PLA films. Electrospun films of PLA/PCL blends demonstrated improved elongation at break while retaining Young’s modulus comparable to that of electrospun PLA films, unlike their solvent-cast counterparts. In contrast, PLA/PEO blends exhibited enhanced hydrophilicity in both processing methods but showed a marked reduction in mechanical properties. In summary, electrospun films consistently outperformed solvent-cast films in terms of flexibility and mechanical integrity, primarily due to their fibrous structure, suppressed phase separation, and reduced crystallinity. This study uniquely demonstrates that electrospinning enables the fabrication of phase-separated PLA/PEO blends with mechanical integrity despite PEO’s inherent immiscibility with PLA and incompatibility in the solvent mixture. Furthermore, electrospinning proves to be an effective processing method for producing PLA blend films with enhanced flexibility and hydrophilicity without the need for plasticizers or compatibilizers.

For a coaxial electrospun drug delivery system (DDS), tuning the permeability of the shell is a promising strategy to achieve controlled drug release. Herein, we fabricated a coaxial electrospun DDS whose shell consisted of PLA and PEO and whose core contained gentamicin sulfate (GS) and PEO, and systematically investigated how the weight ratio of PLA to PEO and molecular weights of PEO (100, 10, and 1 kDa) in the shell modulated the release behavior of GS. Specifically, specimens with and without border heat pressing were prepared for comparison. Increasing the content of PEO (100 kDa) increased the water-soluble content of the PLA/PEO fibers. Notably, PEO with higher molecular weights at the same PEO content resulted in higher water-soluble contents. Kinetic modeling of in vitro drug release showed that specimens prepared without border heat pressing, in which GS could be released from the edges of cut specimens, deviated from Fickian diffusion, while heat-pressed border specimens exhibited first-order kinetics. Fitting the release data of heat-pressed border specimens to the Korsmeyer–Peppas model showed that increasing the content of PEO (100 kDa) decreased the release exponent and increased the rate constant, indicating enhanced diffusion and faster release. The analysis also suggested that formulations containing low-molecular-weight PEO (1 kDa) exhibited more restricted diffusion and a lower rate constant compared to high-molecular-weight PEO. In vitro antibacterial activity against E. coli was consistently effective across all groups, likely due to saturation of the antibacterial effect, whereas inhibition against S. aureus varied with shell composition and closely followed the drug release kinetics. These findings highlight the importance of PEO content and PEO molecular weight in designing coaxial electrospun DDSs with tunable release behavior.