Nanofiber patches offer new opportunities for transdermal drug delivery routes. In this study, we electrospun (polyvinyl alcohol/gelatin)-(polyvinyl alcohol/chitosan), (PVA/G)-(PVA/Cs), core-sheath nanofiber patches (NFPs) containing folic acid (FA) doses, with the vitamin incorporated in different locations of the nanofibers. The morphological and chemical properties of NFPs were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and water contact angle (WCA) analysis. In vitro studies were carried out to evaluate the degradation profile of the nanofiber patches, the cumulative release of folic acid, and the cytotoxicity of the nanofibers. The kinetics of folic acid FA release were analyzed using four well-established mathematical models: zero-order, first-order, Korsmeyer-Peppas, and Higuchi. SEM analysis revealed that the average diameter of the nanofibers ranged between 58 and 87 nm, while TEM imaging confirmed the formation of a distinct core–sheath structure. Water contact angle (WCA) measurements indicated an increase in nanofiber hydrophilicity with higher folic acid content, as evidenced by a decrease in WCA from 45° to 34°. The degradation profile of the core-sheath nanofibers exhibited a biphasic pattern, characterized by rapid initial degradation within the first 5 min (58–61% weight loss), and followed by a slower phase leading to 96% weight loss after 480 min. In vitro release studies demonstrated that nanofibers with FA localized in the sheath layer (PVA/chitosan) exhibited a faster release rate, achieving up to 71% release within the first 15 min. However, distributing folic acid across both the core and sheath layers allowed for a more controlled and sustained release profile. Kinetic modeling revealed that the Korsmeyer-Peppas model provided the best fit for the release data, with the calculated diffusion exponent (n) indicating Fickian diffusion as the dominant release mechanism. Additionally, MTT assay results confirmed the cytocompatibility of the nanofibers, showing over 98% viability in L929 fibroblast cell lines. These findings suggest that electrospun (PVA/gelatin)-(PVA/chitosan) core-sheath nanofibers hold significant potential as a transdermal delivery system for vitamins, including folic acid.
