Synthesis and in vitro characterization of a poly(acrylic acid)-homocysteine conjugate.
It was the aim of this study to improve our knowledge on thiolated polymers by the synthesis and in vitro characterization of a poly(acrylic acid)-homocysteine conjugate. Mediated by a carbodiimide, homocysteine was therefore covalently attached to poly(acrylic acid) via the formation of an amide bond. The isolated conjugate displayed 930 micromol +/- 83 micromol sulfur atoms per gram polymer. Of these thiol groups, 80.1% were oxidized to disulfide bonds during the coupling reaction. In aqueous solutions the conjugate was rapidly oxidized by the formation of disulfide bonds at pH 8, whereas it remained stable at pH 7 and below during the observation period of 4 hours. Due to the immobilization of thiol groups on the polymer, the mucoadhesive and cohesive properties of poly(acrylic acid) were strongly improved. Furthermore, the thiolated polymer exhibited a significantly (p < 0.05) improved permeation enhancing effect in comparison to the unmodified polymer. Because of these features the poly(acrylic acid)-homocysteine conjugate seems to represent a promising novel tool, which might be useful in particular for aqueous formulations based on thiomers.
Bernkop-Schnürch
Andreas
A
Institute of Pharmacy, Department of Pharmaceutical Technology, Leopold-Franzens-University Innsbruck, Innsbruck, Austria. andreas.bernkop@uibk.ac.at
Leitner
Verena
V
Moser
Verena
V
D000180:Acrylic Resins / Q000138:chemical synthesis* / Q000737:chemistry*; D000269:Adhesives; D000465:Algorithms; D004220:Disulfides / Q000138:chemical synthesis; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D010539:Permeability; D012995:Solubility; D013607:Tablets; D013718:Tensile Strength
D000180:Acrylic Resins; D000269:Adhesives; D004220:Disulfides; D013607:Tablets; D006710:Homocysteine