Effect of solvent selection on the morphology and release profiles of vitamin D3-loaded Poly(ε-caprolactone) electrospun fibers: In-silico and experimental study

During the electrospinning process, the choice of solvent significantly influences the size, surface morphology, mechanical properties, and drug delivery efficiency of electrospun fibers. This study investigates the effects of 2,2,2-trifluoroethanol (TFE) and a binary system of dichloromethane (DCM) and N,N-dimethylformamide (DMF) on the characteristics of poly(ε-caprolactone) (PCL, Mn = 80,000 g/mol) fibers loaded with vitamin D3 (VD3) from In-Silico and experimental perspectives. Electrospun fibers produced using DCM:DMF (80:20) exhibited larger diameters (2.53 ± 0.60 μm), greater roughness (17.90 nm), and higher interconnectivity due to DCM´s high volatility. In contrast, fibers spun using TFE showed smaller diameters (1.53 ± 0.50 μm), lower roughness (15.70 nm), and reduced size dispersion, attributed to the solvent's low surface tension and higher dielectric constant. Spectroscopic analyses (UV–Vis and 1H-NMR) confirmed the encapsulation of VD3 within the PCL fibers, demonstrating successful drug integration into the polymer matrix. VD3 release profiles indicated that fibers produced with DCM/DMF provided a more controlled release, with minimal differences between high (log K = -0.48; K = 0.33) and low (log K = -0.66; K = 0.22) VD3 concentrations. In contrast, TFE fibers exhibited higher release rates at high VD3 concentrations (log K = -0.072; K = 0.93) than low concentrations (log K = -0.63; K = 0.24). This behavior is attributed to the excellent VD3 retention in the DCM/DMF system and a more sustained release, supported by theoretical calculations of the interaction energy between PCL and VD3, solvation effects, and thermodynamic properties. Both systems achieved complete release over a similar timeframe, demonstrating consistent and prolonged behavior. Mechanical characterization revealed that TFE-derived fibers were stiffer (elastic modulus: 112.70 MPa) due to improved chain alignment, whereas VD3 acted as a plasticizer, reducing stiffness in both solvent systems. These findings underscore the critical role of solvent selection in tailoring electrospun fibers for controlled drug delivery, highlighting the importance of balancing morphological, mechanical, and release properties to optimize therapeutic applications.