Enhanced pH-responsive 5-FU release from electrospun PLA/PEG fibers incorporating a fluorinated covalent organic framework

• Fluorinated COFs enabled high loading of hydrophilic 5-FU into PLA/PEG fibers • 5-FU@COF incorporation suppressed drug recrystallization and phase separation during electrospinning • 5-FU@COF/fibers showed improved thermal stability and flexibility • 5-FU@COF/fibers exhibited enhanced pH-responsive drug release in pH 5.4 compared to pH 7.4 • COF-polymer composite offer a sustainable platform for potential anticancer drug delivery applications Electrospinning of bio-based poly(lactic acid) (PLA) is a straightforward approach for encapsulating hydrophilic bioactive compounds within biodegradable polymers for sustained release. PLA offers good mechanical properties, biocompatibility, and non-toxic degradation under physiological conditions. However, its intrinsic hydrophobicity hinders the uniform dispersion of hydrophilic drugs, leading to recrystallization, phase separation, and incomplete drug dissolution. In this study, a fluorinated covalent organic framework (COF) was employed as a nanocarrier to encapsulate the hydrophilic anticancer drug, 5-fluorouracil (5-FU), within electrospun PLA fibers containing polyethylene glycol (PEG) as a compatibilizer. The fluorinated COF achieved a 5-FU loading of 65%, enabling efficient drug incorporation within electrospun PLA/PEG fibers, while suppressing drug recrystallization and achieving sustained, pH-responsive release. Compared to directly loaded fibers, the 5-FU@COF/fibers exhibited enhanced cumulative release at acidic pH (pH 5.4) compared to physiological pH (pH 7.4), due to the pH-induced degradation of both the COF and PLA/PEG fibers. Furthermore, embedding 5-FU@COF particles within the fibrous matrix reduced burst release and provided sustained release in aqueous environments. The presence of COF increased the maximum degradation temperature of the fibers, enhancing the thermal stability of the fiber composite. Additionally, the lowered initial degradation temperature of 5-FU/COF fibers at 200°C relative to drug-free COF/fibers served as a clear indicator of successful drug loading. Overall, these findings establish pH-responsive COF-polymer composites as a sustainable platform for selective anticancer drug delivery in acidic conditions.