2010-Jordan-对比Hepa和DCB6-03-10].pdf

Comparative Study of Chemoembolization Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere Loaded with Doxorubicin and Irinotecan Olivier Jordan, PhD, Alban Denys, MD, Thierry De Baere, MD, Nathalie Boulens, and Eric Doelker, PhD PURPOSE: To characterize in vitro the loadability, physical properties, and release of irinotecan and doxorubicin from two commercially available embolization microspheres. MATERIALS AND METHODS: DC Bead (500–700 m) and Hepasphere (400–600 m) microspheres were loaded with either doxorubicin or irinotecan solutions. Drug amount was quantified with spectrophotometry, bead elasticity was measured under compression, and bead size and loading homogeneity were assessed with microscopy image analysis. Drug release was measured over 1-week periods in saline by using a pharmacopeia flow-through method. RESULTS: Almost complete drug loading was obtained for both microsphere types and drugs. Doxorubicin-loaded DC Beads maintained their spherical shape throughout the release. In contrast, Hepaspheres showed less homoge- neous doxorubicin loading and, after release, some fractured microspheres. Incomplete doxorubicin release was observed in saline over 1 week (27% 2 for DC beads and 18% 7 for Hepaspheres; P .013). About 75% of this amount was released within 2.2 hours for both beads. For irinotecan, complete release was obtained for both types of beads, in a sustained manner over 2–3 hours for DC Beads, and in a significantly faster manner as a 7-minute burst for Hepaspheres. CONCLUSIONS: The two drug-eluting microspheres could be efficiently loaded with both drugs. Incomplete doxorubicin release was attributed to strong drug-bead ionic interactions. Weaker interactions were observed with irinotecan, which led to faster drug release. J Vasc Interv Radiol 2010; 21:1084–1090 TRANSARTERIAL chemoembolization