Hydrogels Based on Poly(Ether-Ester)s as Highly Controlled 5-Fluorouracil Delivery Systems—Synthesis and Characterization
Open Access
- 28 December 2020
- Vol. 14 (1), 98
- https://doi.org/10.3390/ma14010098
Abstract
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 ε‑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, ε‑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 °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.This publication has 42 references indexed in Scilit:
- New Insights into the RNA-Based Mechanism of Action of the Anticancer Drug 5′-Fluorouracil in Eukaryotic CellsPLOS ONE, 2013
- Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A reviewJournal of Controlled Release, 2012
- Preparation of new 5-fluorouracil-loaded zein nanoparticles for liver targetingInternational Journal of Pharmaceutics, 2011
- 5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in miceBMC Cancer, 2010
- Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogelBMC Cancer, 2010
- Injectable and thermosensitive poly(organophosphazene) hydrogels for a 5‐fluorouracil deliveryJournal of Applied Polymer Science, 2009
- 5-Fluorouracil: Mechanisms of Resistance and Reversal StrategiesMolecules, 2008
- Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivoNucleic Acids Research, 2006
- Poly(d,l-lactide-ran-ε-caprolactone)-poly(ethylene glycol)-poly(d,l-lactide-ran-ε-caprolactone) as parenteral drug-delivery systemsBiomaterials, 2004
- Stereoselective polymerization of racemic dl-lactide in the presence of butyllithium and butylmagnesium. Structural investigations of the polymersPolymer, 2000