No abstract

The sustained release of alprenolol, a β-adrenergic antagonist, could be beneficial for the treatment of various heart diseases while reducing the side effects resulting from its continuous use. The novel and branched copolymers uniquely composed of biodegradable components (lactide and glycolide) have been synthesized using natural and therapeutically-efficient β-aescin-initiator, and consequently characterized to determine their structures and physicochemical properties. The obtained matrices were not cyto-and genotoxic towards bacterial luminescence, protozoan, and Salmonella typhimurium TA1535. The copolymers release the drug in vitro in a sustained manner and without burst release. The value of the drug released was strongly dependent on the copolymer composition and highly correlated with the hydrolytic matrices' degradation results.

Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used nontoxic β-cyclodextrin (β-CD) as effective, simple, inexpensive, and safe for the human body initiator for the synthesis of biocompatible and biodegradable functionalized polymers suitable for the medical and pharmaceutical applications. The obtained polymeric products were synthesized through a ring-opening polymerization (ROP) of ε-caprolactone (CL), d,l-, and l,l-lactide (LA and LLA). The chemical structures of synthesized materials were elucidated based on 1H NMR and solid-state carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR) analysis, while the incorporation of β-CD molecule into the polymer chain was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, molecular modeling has been applied to investigate the intrachain rigidities and chain architectures for several representative structures. The obtained and thoroughly characterized branched matrices were then used to generate the first β-cyclodextrin/biodegradable polymer/β-blocker conjugate through the successful conjugation of pindolol. The conjugates were fabricated by carbodiimide-mediated coupling reaction. The branched biodegradable materials released the drug in vitro in a sustained manner and without “burst release” and thus have the ability to treat different heart diseases.

No abstract

Związki o zróżnicowanej budowie, których wspólną cechą jest obecność grupy adamantylowej w cząsteczce, są stosowane w leczeniu poważnych schorzeń neurologicznych, takich jak choroba Parkinsona, choroba Alzheimera, a także w terapii cukrzycy typu 2 oraz jako leki przeciwwirusowe. W przypadku prostych aminowych pochodnych adamantanu grupa adamantylowa bezpośrednio odpowiada za działanie lecznicze substancji. W innych przypadkach pełni funkcję usztywniającą cząsteczkę, zapobiegając niekorzystnym reakcjom wewnątrzcząsteczkowym. Nowe pochodne zawierające grupę adamantylową, tworzone jako potencjalne substancje lecznicze są obecnie badane w aspekcie aktywności przeciwmalarycznej i przeciw wirusom HIV.