Folic acid-containing nanofibers by simultaneous process for transdermal drug delivery:  preparation, characterization, and in vitro biocompatibility

Abstract Nanofibers with bioactive agents are good candidates for skin-care applications due to high spesific surface area, low density and highly porous structure. In this study, hydrophilic based bioactive nanofibers were produced via an electrospinning and electrospraying simultaneous process. Polyvinyl alcohol (PVA), polyvinyl alcohol-gelatin (PVA-Gel) and polyvinyl alcohol-alginate (PVA-Alg) polymers were used as the matrix material and folic acid (FA) particles were dispersed simultaneously on the surface of these hydrophilic nanofibers. The morphology of the nanofibers (NFs) was uniform and dispersed folic acid particles incorporated into the structure of nanofibers as confirmed by scanning electron microscopy (SEM). Thermal behavior, chemical structure of the composite nanofibers were analyzed/investigated by thermogravimetric analysis (TGA) and Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) which showed that no chemical bonding between vitamin and polymers. A controlled release of FA-loaded electrospun fibers were carried out by UV-Vis in vitro study within the 8 hour-period in artificial sweat solutions (acidic media, pH 5,44). The obtained PVA/FA, PVA-Gel/FA and PVA-Alg/FA fibers released 49.6 %, 69.55 % and 50.88 % of the sprayed FA in 8 h, indicating the influence of polymer matrix and polymer-drug interactions, on its release from the polymer matrix. Moreover, biocompatibility of all developed novel NFs was assessed by two different cytotoxicity tests,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and neutral red uptake (NRU) assay in L929 cell lines. In all cases, it is clearly concluded that these new electrospun fibers had fast-release of the vitamin and the hybrid process is suitable for transdermal patch applications, especially for skin-care products. Moreover, it has been proposed nanofiber with folic acid as a patch may prevent the COVID-19. The results of cytotoxicity assays on L929 cell reveal that all prepared NFs have no or slight cell toxicity. PVA and PVA-Gel with/without FA nanofibers seems more biocompatible than PVA-Alg nanofibers.