Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids--Synthesis, Characterization, and in Vitro Release Study.
Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance ((1)H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer's rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule.
Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. eoledzka@wum.edu.pl.
Ewa
E
Oledzka
Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. sawicka.anna.maria@gmail.com.
Anna
A
Sawicka
Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. marcin.sobczak@wp.pl.
Marcin
M
Sobczak
Department of Environmental Health Science, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. gnalecz@wum.edu.pl.
Grzegorz
G
Nalecz-Jawecki
Department of Environmental Health Science, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. agata.skrzypczak@wum.edu.pl.
Agata
A
Skrzypczak
Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. waclaw.kolodziejski@wum.edu.pl.
Waclaw
W
Kolodziejski
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry; D048908:Aliivibrio fischeri / Q000187:drug effects; D000596:Amino Acids / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002208:Caproates / Q000737:chemistry; D016798:Ciliophora / Q000187:drug effects; D002956:Citrulline / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D007093:Imidazoles / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D019906:Nuclear Magnetic Resonance, Biomolecular; D011091:Polyesters / Q000737:chemistry*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000596:Amino Acids; D000959:Antihypertensive Agents; D002208:Caproates; D007093:Imidazoles; D007783:Lactones; D011091:Polyesters; D002956:Citrulline; C033616:poly(lactide); C121056:caprolactone; C006900:N,N-carbonyldiimidazole; D001120:Arginine; D011224:Prazosin
biodegradable polymers; controlled release/delivery; cytotoxicity; macromolecular drug delivery; polymeric drug delivery system; prazosin