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.