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

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.

Synthesis and Characterization of New Biodegradable Injectable Thermosensitive Smart Hydrogels for 5-Fluorouracil Delivery

“…The concentrations of 5-FU released were determined using HPLC, as previously described by our team [ 8 ]. In brief, the Hitachi Chromaster chromatograph was used, which included a pump type 5160, autosampler model 5260, thermostat 5310, and DAD-detector UVD 5430.…”

“…One strategy for increasing therapy effectiveness is to limit the distribution of cytostatics to the target tissue, which reduces systemic toxicity while also ensuring a sufficient drug concentration in the tumor. This strategy can be carried out by employing novel polymeric local drug delivery systems (LDDSs) [ 3 , 4 ], such as micro- and nanoparticles [ 5 , 6 ], micelles [ 7 , 8 ], or hydrogels [ 7 , 8 ]. Hydrogels are defined as three-dimensional, crosslinked structures able to absorb large amounts of water or body fluids while maintaining integrity [ 9 , 10 ].…”

Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment

“…As a result, the measurement of both 5-FU and MTX in a mixture had an overlapped peak. A new derivative UV-spectrophotometric method was developed and validated by the authors [42,43] for drug quantification. To make sure that the whole drug mixture was released and there are no destructions or engagements of any of them by the constructed hydrogel system, the release experiment was allowed to continue until the complete release of the loaded drug mixture.…”

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

“…The 13 C spectra: 75.4 MHz, 5 s repetition time, 1.4 s acquisition time, 20,000 scans per each spectrum. Percentage molar value of PEG in a copolymer chain were estimated using the following formulas [64]:…”