Hydrogels Based on Poly(Ether-Ester)s as Highly Controlled 5-Fluorouracil Delivery Systems-Synthesis and Characterization

A novel and promising hydrogel drug delivery system (DDS) capable of releasing 5-fluorouracil (5-FU) in a prolonged and controlled manner was obtained using epsilon-caprolactone-poly(ethylene glycol) (CL-PEG) or rac-lactide-poly(ethylene glycol) (rac-LA-PEG) copolymers. Copolymers were synthesized via the ring-opening polymerization (ROP) process of cyclic monomers, epsilon-caprolactone (CL) or rac-lactide (rac-LA), in the presence of zirconium(IV) octoate (Zr(Oct)(4)) and poly(ethylene glycol) 200 (PEG 200) as catalyst and initiator, respectively. Obtained triblock copolymers were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the structure and tacticity of the macromolecules were determined. The relationship between the copolymer structure and the reaction conditions was evaluated. The optimal conditions were specified as 140 degrees C and 24 h. In the next step, CL-PEG and rac-LA-PEG copolymers were chemically crosslinked using hexamethylene diisocyanate (HDI). Selected hydrogels were subjected to in vitro antitumor drug release studies, and the release data were analyzed using zero-order, first-order, and Korsmeyer-Peppas mathematical models. Controlled and prolonged (up to 432 h) 5-FU release profiles were observed for all examined hydrogels with first-order or zero-order kinetics. The drug release mechanism was generally denoted as non-Fickian transport.

Automated summary

A novel hydrogel drug delivery system capable of prolonged and controlled release of 5-FU was developed using CL-PEG and rac-LA-PEG copolymers, which were synthesized through the ring-opening polymerization process. The copolymers were chemically crosslinked and exhibited controlled release profiles with first-order or zero-order kinetics. The release mechanism was generally categorized as non-Fickian transport, showing potential for future applications in drug delivery.