Development of Eudragit L100/sodium alginate-carrageenan core/shell nanofiber patches for dermal delivery of omega-3 acid ethyl ester.
Abstract
Oxidation-prone omega-3 acid ethyl esters offer biologically attractive lipid cues for skin repair and dermocosmetic applications; however, their topical translation is constrained by poor aqueous compatibility, chemical lability, and limited residence at the skin interface. Herein, a coaxially electrospun core-shell nanofiber patch was developed to compartmentalize docosahexaenoic/eicosapentaenoic acid (DHA/EPA)-containing omega-3 ethyl esters within an Eudragit L100 (EL100) core while presenting a sodium alginate-κ-carrageenan (SA-CRG) polysaccharide shell. Electrospinning parameters were systematically optimized by tuning the EL100 concentration, the ethanol/N,N-dimethylformamide ratio, and the core/shell flow rates, yielding smooth, bead-free fibers with a continuous core-shell architecture, as verified by SEM and TEM. Although Ca2⁺-mediated ionic crosslinking enhanced shell compactness and tensile integrity, FTIR/DSC and surface-wettability changes indicated DHA/EPA oxidation and lipid redistribution during aqueous post-treatment; therefore, the non-crosslinked 25EL100(5:5)-DHA + EPA/SA-CRG mats were selected for delivery and biological evaluation. The optimized fibers combined a hydrophilic skin-contacting surface with controlled swelling at pH 4.0 and sustained omega-3 release over 120 h, reaching cumulative DHA and EPA release of 88.5% and 72.9%, respectively. Release kinetics were best described by the Korsmeyer-Peppas model (R2 = 0.9912 for DHA; R2 = 0.9884 for EPA), with n values below 0.45, indicating predominantly diffusion-governed transport. The nanofibers were cytocompatible with human dermal fibroblasts, maintaining 91.81% viability for the DHA/EPA-loaded formulation versus 97.65% for the placebo, and promoted fibroblast wound-closure behavior in scratch assays. Complementary microplate-based turbidimetric assays further indicated that the antibacterial performance of the DHA/EPA-loaded mats was influenced by lipid oxidative status. Oxidized DHA/EPA-loaded mats exhibited concentration-dependent suppression of bacterial growth, with a stronger effect against the Gram-positive Staphylococcus aureus than against the Gram-negative Escherichia coli, whereas non-oxidized mats showed weaker activity. Overall, EL100/SA-CRG core-shell nanofibers provide a dry, handleable, and biologically tolerated platform for sustained topical delivery of labile omega-3 ethyl esters, thereby supporting their further development as advanced dermal patches for skin repair and dermocosmetic applications.