Polymer–cysteamine conjugates: new mucoadhesive excipients for drug delivery?

Abstract

In the present study, the features of two new thiolated polymers—the so-called thiomers—were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC–cysteamine conjugate and PCP–cysteamine conjugate showed in maximum 43±15 and 138±22 μmole thiol groups per g polymer (mean±S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC–cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly ( P<0.01) improved mucoadhesion, whereas, the mucoadhesive properties of the PCP–cysteamine conjugate were increased 2.5-fold compared with the unmodified polymer. The swelling behaviour of the CMC–cysteamine conjugate was uninfluenced by the covalent attachment of the sulfhydryl compound. In contrast the swelling behaviour of the PCP–cysteamine conjugate was improved significantly ( P<0.01) versus unmodified PCP. Furthermore, in aqueous solutions the disintegration time of tablets based on the CMC– and PCP–cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP–cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.