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

Area of Science:

• Polymer Chemistry
• Materials Science
• Drug Delivery Systems

Background:

• Hydrogels offer potential for controlled drug release.
• Developing novel copolymers is crucial for advanced drug delivery systems (DDS).
• 5-fluorouracil (5-FU) is a key chemotherapeutic agent requiring effective delivery.

Purpose of the Study:

• To synthesize and characterize novel ε‑caprolactone‑poly(ethylene glycol) (CL-PEG) and rac‑lactide-poly(ethylene glycol) (rac-LA-PEG) copolymers.
• To develop a hydrogel drug delivery system (DDS) for prolonged and controlled release of 5-fluorouracil (5-FU).
• To evaluate the in vitro drug release kinetics and mechanism.

Main Methods:

• Copolymer synthesis via ring-opening polymerization (ROP) using ε‑caprolactone (CL) or rac-lactide (rac-LA) with PEG 200 and a zirconium catalyst.
• Characterization using Nuclear Magnetic Resonance (NMR) and Gel Permeation Chromatography (GPC).
• Chemical crosslinking of copolymers with hexamethylene diisocyanate (HDI) to form hydrogels.
• In vitro drug release studies of 5-FU and kinetic analysis using mathematical models (zero-order, first-order, Korsmeyer-Peppas).

Main Results:

• Triblock copolymers CL-PEG and rac-LA-PEG were successfully synthesized and characterized.
• Optimal synthesis conditions identified as 140 °C for 24 hours.
• Hydrogels exhibited controlled and prolonged 5-FU release for up to 432 hours.
• Drug release kinetics followed first-order or zero-order models, indicating non-Fickian transport.

Conclusions:

• Novel CL-PEG and rac-LA-PEG based hydrogels are effective for sustained 5-FU delivery.
• The developed hydrogels demonstrate potential as promising drug delivery systems for cancer therapy.
• Understanding the release kinetics and mechanism is vital for optimizing DDS performance.