Development of electrospun poly (vinyl alcohol) nanofiber oral film containing zolmitriptan for sublingual delivery: optimization, ex-vivo permeability and in-vitro cytotoxicity study

Zolmitriptan (ZLT), a 5-HT1B/1D serotonin receptor agonist, is commonly used in the treatment of migraine. However, ZLT suffers from low oral bioavailability due to extensive hepatic metabolism, being a BCS class III drug (highly soluble, low permeability), and having a short biological half-life. To address these limitations, there is increasing interest in alternative routes and delivery systems to enhance ZLT's therapeutic efficacy. This study aimed to develop a ZLT-loaded electrospun poly(vinyl alcohol) (PVA) nanofiber oral film to improve its biopharmaceutical properties. The film was prepared using the ESPIN-NANO electrospinning device, incorporating PVA, PEG 400, citric acid, methyl paraben and sucrose, with optimization based on a 24 full factorial design. The optimized film exhibited a smooth surface, cylindrical shape and a non-beaded, non-porous structure with an average diameter of 258±30 nm and an entrapment efficiency of 97.25%. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies confirmed the amorphization of ZLT. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy indicated no chemical interactions between ZLT and the polymer. Ex-vivo permeability studies on palatal goat mucosa using a Franz diffusion cell demonstrated 100% permeability of the ZLT-loaded nanofiber film within 300 seconds. In-vitro cytotoxicity testing on human oral epithelial cells (TR146 cells) using the MTT assay showed no significant cytotoxicity. This innovative approach offers a potentially effective and beneficial method for delivering ZLT in migraine therapy.