Beyond the shell: exploring polymer–lipid interfaces in core–shell nanofibers to carry hyaluronic acid and β-caryophyllene

Hyaluronic acid (HA) and β-caryophyllene (βCp) are two promising agents in biomedical research, each offering unique therapeutic benefits. The successful integration of these compounds into a single, functional nanofiber system presents a significant technical challenge, demanding innovative strategies to ensure their compatibility and sustained activity. This study addresses this critical challenge through the rational design and fabrication of hybrid core–shell nanofibers manufactured via coaxial electrospinning. Poly(lactic acid) (PLA) was used as an outer shell providing structural integrity and effectively encapsulating a core comprising a nanoemulsion containing β-caryophyllene (NE-βCp) alongside HA. A rigorous optimization of the electrospinning process was critical, involving the systematic evaluation of key parameters. This optimization successfully identified the optimal core formulation (1% w/w HA, 2% w/w NE) and process parameters (17 kV applied voltage, 6.25 flow rate ratio (0.04 mL/h inner; 0.25 mL/h outer), 12 cm needle-to-collector distance). These conditions provided highly uniform fibers with an average diameter of 439 ± 100 nm, notably 37% larger than fibers without the lipid core. Furthermore, maintaining ambient relative humidity below 45% proved essential for processing stability. Comprehensive morphological characterization via scanning electron microscopy confirmed the uniformity of the fibers. At the same time, confocal microscopy, cross-sectional imaging, and attenuated total reflectance with Fourier transform infrared (ATR-FTIR) spectroscopy provided compelling evidence for the successful formation of the intended core–shell structure. The resulting nanofibers exhibited surface hydrophobicity, suggesting potential for anti-adhesive membrane applications. Thermal and crystalline analyses demonstrated improved thermal stability upon NE-βCp incorporation. Collectively, these results provide robust evidence for the feasibility of producing multifunctional nanofiber membranes that successfully integrate a polymer–lipid hybrid core encapsulated within a PLA shell, highlighting substantial potential for biomedical applications by overcoming key material integration hurdles.