Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.

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.