Objective: To prepare a new doxorubicin-gelatin-microspheres (DR-GMs) suitable for hepatic artery chemoembolization.
Methods: Oxidized dextran and glutaraldehyde were used respectively as crosslinking agent for preparing DR-GMs. Orthogonal design was employed to optimize the preparation of the oxidized dextran cross-linked GMs. The morphology, swelling, and in vitro and in vivo degrading were compared between the two groups of microspheres, both with 60% degree of cross-linking.
Results: The granulometers of both groups of microspheres fitted for hepatic artery embolization. The roundness of the microspheres (observed with scanning electron microscope) crosslinked by oxidized-dextran was better than those crosslinked by glutaraldehyde. The microspheres crosslinked by oxidized-dextran had an average diameter of (78.2 +/- 8.1) microm, and a narrow size distribution (76.4 +/- 3.2)%, which ranged from 50 to 125 microm. The drug content rate and encapsulation rate of the microspheres crosslinked by oxidized-dextran were (87.5 +/- 0.9)% and (12.2 +/- 1.1)% respectively, higher than those crosslinked by glutaraldehyde (P < 0.01). The cumulative release rate of doxorubicin from the microspheres crosslinked by oxidized-dextran in 12 hours was 83.2%, lower than that from the microspheres crosslinked by glutaraldehyde (P < 0.01). The in vitro and in vivo studies found that the duration of degradation of the microspheres crosslinked by oxidized-dextran appeared longer than those crosslinked by glutaraldehyde.
Conclusion: Oxidized-dextran is a better crosslinking agent for preparing DR-GMs, because it has more advantages over glutaraldehyde as for hepatic artery chemoembolization.