Slow Release Drug Based on Hydroxyurea/Chitosan Cross-Linked Matrix

Abstract

Hydroxyurea (HU), also known as hydroxycarbamide, is an effective anticancer drug. The present work is based on partially crosslinked chitosan with glutaraldehyde in the presence of hydroxyurea. The obtained embedded HU in the cross-linked matrix was evaluated as a controlled-release drug based on the swelling mechanism. The swelling study was carried out in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and deionised water. The % of swelling at equilibrium for the 0.25% crosslinking density after 24 h of immersion was: 200, 150, and 100% in SGF, H2O and SIF medium, respectively. The concentration of the released drug HU from the chitosan matrix in the different media was determined by UV spectroscopy at λmax at 208.5 nm as a function of time. The release rate of HU from the matrix increases with the swelling rate of the partially cross-linked chitosan. The loading capacity of the prepared gel was 33.3% by weight. The loading capacity and the rate of HU release were found to be inversely affected by the high degrees of crosslinking and increased with increasing the degree of hydrogel swelling. In addition, the rate of HU release was higher at lower pH levels. The study showed that the HU released from the hydrogel matrices in SGF reached 75 and 88.3% of the loaded HU within 8 and 24 h, respectively. This is almost twice the reported value in the literature based on polyphosphate‐anion‐crosslinked chitosan microspheres.