In this study, non-toxic, biodegradable, and pH-sensitive polyurethane hydrogels (PUs) were prepared by using hexamethylene diisocyanate (HDI), copolymers of є-caprolactone (CL), rac-lactide (LA), and poly(ethylene glycol) (PEG), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-bPPO-b-PEO), 1,4-butanediol (BD), and L-glutamine (Gln). The CL, LA, and PEG copolymers were obtained in the presence of a new synthesized catalytic system: diethylzinc/ethyl-3,4-dihydroxybenzoate. Obtained PUs were screened for their cytotoxicity, evaluated for their swelling behavior and hydrolytic degradation, and employed as hydrogel pH-responsive anti-cancer drug delivery systems (DDSs). The novel and promising hydrogel DDSs, capable of releasing 5-fluorouracyl (5-FU) and fluorodeoxyuridine (5-fluoro-2′-deoxyuridine, FUdR) in a sustained and controlled manner, were prepared and were nontoxic. Most prepared hydrogel DDSs were found to release anti-cancer drugs with first-order or zero-order kinetics. The drug release mechanism was generally denoted as Fickian or non-Fickian transport. The possibility of controlling the kinetics of drug release by changing the pH of the environment was also observed. The findings indicate that these PU hydrogels are suitable for use as intelligent DDSs for the targeted delivery of 5-FU or FUdR. We expect that the hydrogel DDSs developed will be utilized in the treatment of pancreatic cancer.

Microwave-assisted enzymatic ring-opening polymerization (eROP) has emerged as a promising green approach for the synthesis of biomedical polymers with potential applications in drug delivery systems and implantable biomaterials. This review provides a critical overview of the current state of microwave-assisted eROP, with particular emphasis on systems catalyzed by Candida antarctica lipase B (CALB), the most widely used biocatalyst in this field. The fundamental aspects of CALB-catalyzed polymerization, including its catalytic mechanism and key parameters influencing reaction efficiency, are discussed under both conventional and microwave-assisted conditions. Microwave irradiation can offer significant advantages, such as reduced reaction times, improved energy efficiency, and, in some cases, enhanced polymer properties, including higher molecular weight and narrower dispersity. However, its effects are strongly dependent on reaction conditions, including solvent properties, temperature, and enzyme stability, with both accelerating and inhibiting effects reported. The review summarizes the current literature on microwave-assisted eROP of representative cyclic monomers, including ε-caprolactone, ω-pentadecalactone, and L-lactide, highlighting the influence of microwave parameters on polymerization outcomes and material properties. Despite promising results, microwave-assisted eROP remains relatively underexplored, with limited monomer scope and incomplete understanding of microwave–enzyme interactions. Challenges such as enzyme deactivation, lack of standardized methodologies, and scalability issues are also addressed. Overall, microwave-assisted eROP of cyclic monomers represents a sustainable and efficient strategy for producing high-quality pharmaceutical polymers. However, further research is required to fully realize its potential in industrial and biomedical applications.