Optimization of Nanofibers Simulating Lipid Organization of Impaired Human Skin

Abstract

Human skin is an effective barrier due to the stratum corneum, outermost layer, which is commonly described as the \"brick- and-mortar\" model that consisted of corneocytes (bricks) and intercellular lipids (mortar). In healthy skin, the lipid lamella structure is well-organized with a dense orthorhombic lateral packing, whereas the lipid organization in the disordered skin becomes the disrupted and irregular, exhibiting a hexagonal lateral packing which has resulted in a decrease barrier function. While several synthetic membranes or excised human skin can adequately mimic in vitro drug permeation characteristics of healthy skin, there are no equivalent synthetic membranes that reliably replicate the barrier properties of disordered skin. Electrospinning technology offers a distinct advantage over membrane systems, allowing fine-tuned control over pore size and fiber diameter. This study aimed to optimize electrospun nanofibers that simulate the disordered lipid organization of human stratum corneum. For this purpose, the fiber surface morphology was characterized using Scanning Electron Microscopy (SEM), and the disrupted lipid structure in the nanofibers was elucidated using Attenuated Total Reflectance–Fourier Transform Infrared (ATR–FTIR) Spectroscopy and X-Ray Diffractometry (XRD).SEM images revealed that the mean pore sizes of polyurethane/polycaprolactone nanofibers with and without ethyl cellulose were 4.14 ± 0.34 μm and 5.51 ± 0.82 μm, respectively. The average fiber diameters ranged between 0.41 ± 0.11 μm to 1.21 ± 0.32 μm. In the ATR-FT-IR spectra of the electrospun nanofibers, the sharp methylene stretching bands at 2920 and 2850 cm−1 became broader and less intense, accompanied by slight blue shifts (from 2923 to 2926 cm−1 and from 2853 to 2855 cm−1, respectively). These changes were consistent with an increased proportion of gauche conformers, reduced chain-packing regularity, and consequently a disrupted lipid-like structure. In the XRD diffractograms, the reflections of the nanofibers at 21.3° and 23.7° closely resembled those of the parent polymers. On the other hand, the low-angle reflections (2–12°) characteristic of ceramide IIIB, ceramide III, and cholesterol were markedly diminished or absent in the nanofibers. This indicated that the lipid components within the nanofibers were converted to an amorphous state, reflecting disruption of the lipid organization. In conclusion, the optimized nanofibers can stimulate the lipid organization in the impaired human skin.Keywords: Impaired Human Skin, Lipid Organization, Nanofiber, Skin Barrier Function, Stratum Corneum