13th Annual Global Embolization Symposium & Technologies
Purpose : The use of drug eluting beads for treatment of liver tumors is a widely-accepted practice. Non-target ischemic and drug-induced damage to surrounding normal tissue could be potentially reduced if fewer beads were able to deploy the same amount of drug. This study investigated the ability of bioresorbable microspheres, made of chitosan and carboxymethyl cellulose, to load increased amounts of bevacizumab (Avastin, Genentech, SanFrancisco, CA).
Material and Methods : Two methods of increasing the loading of bevacizumab onto bioresorbable microspheres were tested, by increasing loading solution volume and increasing its concentration. Volumes of 0.5mL, 1.0mL, and 2mL loading solution at a concentration of 2mg/mL were used for the increasing volume group. Concentrations of 2mg/mL, 4mg/mL and 8mg/mL at volumes of 0.5 mL were tested for the increasing concentration group; water was used as a diluent. Microspheres were prepared via an inverse emulsion method and sieved to a size of 100μm–300μm. Sample vials containing 50mg (wet weight) of microspheres were incubated in the designated loading solution for two hours at room temperature, with 30uL samples drawn at 10, 30, 60 and 120min. The samples were evaluated for bevacizumab concentration on a BCA protein assay kit (Pierce Biotechnology #23225, Rockford, IL).
Results : Both methods produced significant increases in the amount of bevacizumab that could be loaded per mg of wet microspheres. The increasing volume method significantly increased loading between all three volumes, reaching a maximum of 47.6ug bevacizumab loaded per mg of microspheres (2mL of a 2mg/mL loading solution incubated with 50mg of microspheres for two hours). The highest loading was achieved by increasing the loading solution concentration, which loaded 68.2ug/mg beads (500uL of an 8mg/mL loading solution, incubated with 50mg microspheres for two hours) (Fig. 1). This corresponds to using approximately 75% fewer microspheres to load the same amount of drug.
Conclusions : Significant increases of bevacizumab loading onto bioresorbable microspheres was demonstrated by two methods: increasing the loading solution volume or its concentration. By increasing the amount of drug loaded per bead, we may be able to use significantly fewer microspheres, therefore reducing the ischemic effect of drug eluting particles.