Synthesis and in vitro evaluation of cross-linked Plantago ovata seed nanofibrous implants for sustained release of 5-fluorouracil and caffeine

Cross-linked polysaccharide-based nanofibers were successfully fabricated as controlled drug delivery systems for 5-fluorouracil (5-FU) and caffeine (Caf). Characterization by SEM, FTIR, ^1H NMR, XRD, and elemental analysis confirmed uniform fiber morphology (180–220 nm), efficient drug incorporation, molecular-level drug–polymer interactions, and predominantly amorphous drug dispersion. In vitro release studies demonstrated sustained drug release over 72 h, with Caf showing pH-independent release and 5-FU exhibiting pH-responsive behavior. Kinetic analysis revealed diffusion-controlled Higuchi release under acidic conditions and first-order release under basic conditions (n < 0.5, Korsmeyer–Peppas), with no burst release observed. MTT assay on HepG2 cells indicated enhanced cytotoxicity of 5-FU-loaded nanofibers (CC50 = 7.5 ± 0.2 μM) compared to free 5-FU (CC50 = 14.5 ± 0.4 μM), while blank nanofibers were non-toxic. These results demonstrate that the developed nanofibers are a robust, tunable, and pH-responsive platform for site-specific chemotherapeutic delivery, warranting further in vivo evaluation and mechanistic studies.