Examination of oxidized cellulose as a macromolecular prodrug carrier: preparation and characterization of an oxidized cellulose-phenylpropanolamine conjugate

The purpose of this study was to investigate the use of 6-carboxycellulose (OC), a biocompatible and bioresorbable polymer, as a prodrug carrier for amine drugs. Phenylpropanolamine hydrochloride (PPA. HCl) was used as a model drug. OC and PPA were reacted in dimethylformamide (DMF) in the presence of 1,3-dicyclohexylearbodiimide (DCC) for 2.5 days at room temperature. Filtration, followed by washing with methanol, and subsequent drying, under vacuum, produced the conjugate in 65-78% yield. The amount of PPA in the product, determined from the difference in the carboxylic content before and after the reaction, was 24.2% (w/w), corresponding to a degree of substitution (DS) value of 0.7. The Fourier transform-infra red (FT-IR) spectrum of the conjugate, compared with that of OC and PPA. HCl, showed a new band at about 1533 cm(-1) attributable to a > C=O (amide II) stretching and NI-H (amide I and amide II) bending vibrations, a decrease in intensity of the characteristic free carboxylic acid carbonyl stretching band at about 1748 cm(-1), and a strong band at 1663 cm(-1) due to > C=O (amide I) stretching vibration, suggesting that the OC is linked to PPA via an amide bond. The solid-state carbon-13 cross polarization/magic angle spinning nuclear magnetic resonance ((CCP)-C-13/MAS NMR) spectrum of the conjugate was also consistent with this structure. The release studies performed in pH 4.5, 5.5, and 7.4 buffer solutions and in rat liver homogenate, (pH 7.4), showed the conjugate to be more susceptible to hydrolysis at a lower pH and in the presence of rat liver homogenate. In conclusion, the results presented show that OC can be covalently linked to amine drugs via an amide, bond in DMF using DCC as a coupling agent, and provide a macromolecular prodrug delivery system. (C) 2001 Elsevier Science B.V. All rights reserved.