EGDMA- and TRIM-Based Microparticles Imprinted with 5-Fluorouracil for Prolonged Drug Delivery
Michał Cegłowski, Joanna Kurczewska, Aleksandra Lusina, Tomasz Nazim, Piotr Ruszkowski
Abstract
Imprinted materials possess designed cavities capable of forming selective interactions with molecules used in the imprinting process. In this work, we report the synthesis of 5-fluorouracil (5-FU)-imprinted microparticles and their application in prolonged drug delivery. The materials were synthesized using either ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) cross-linkers. For both types of polymers, methacrylic acid was used as a functional monomer, whereas 2-hydroxyethyl methacrylate was applied to increase the final materials’ hydrophilicity. Adsorption isotherms and adsorption kinetics were investigated to characterize the interactions that occur between the materials and 5-FU. The microparticles synthesized using the TRIM cross-linker showed higher adsorption properties towards 5-FU than those with EGDMA. The release kinetics was highly dependent upon the cross-linker and pH of the release medium. The highest cumulative release was obtained for TRIM-based microparticles at pH 7.4. The IC50 values proved that 5-FU-loaded TRIM-based microparticles possess cytotoxic activity against HeLa cell lines similar to pure 5-FU, whereas their toxicity towards normal HDF cell lines was ca. three times lower than for 5-FU.