117 - Development of Epirubicin-Loaded Lipiodol Beads by Two-Step Membrane Emulsification

Purpose: To characterize the physicochemical properties of novel Lipiodol Beads and to evaluate their in vitro epirubicin release kinetics.

Materials and Methods: Lipiodol Beads were developed using a two-step membrane emulsification method (i.e., W/O/W type multiple emulsion): first through a hydrophobic membrane to form a W/O emulsion, followed by passage through a hydrophilic membrane to produce Lipiodol droplets with a bead-like morphology. The droplet shape was stabilized using a gelatin solution as the external aqueous phase. Droplet morphology and size distribution (D10/D50/D90) were assessed by laser diffraction particle analysis and optical microscopy. In vitro epirubicin release was quantified by UV-Vis spectrophotometry and the release kinetics were compared with conventional W/O emulsion by using a two-way mixed repeated-measures ANOVA. For in vivo evaluation in a rat HCC model, micro-CT and H&E histology were performed immediately after intra-arterial delivery of both formulations.


Results: Epirubicin-loaded Lipiodol Beads exhibited a narrow size distribution (D10 66.70 ± 4.91 µm; D50 107.38 ± 10.9 µm; D90 166.02 ± 18.35 µm). On microscopy, epirubicin was consistently localized within Lipiodol Beads. Release from Lipiodol Beads was significantly slower compared with W/O emulsions (P=0.001), with a significant time × group interaction (P< 0.001). In vivo imaging showed greater Lipiodol deposition in tumors treated with Lipiodol Beads. Histopathology demonstrated clearer ischemic changes and accumulation of Lipiodol droplets within intratumoral microvasculature and peritumoral portal venous branches.

Conclusion: Epirubicin-loaded Lipiodol Beads were successfully prepared with uniform size distribution and stable drug encapsulation. They exhibited slower in vitro epirubicin release, and preliminary in vivo data suggest enhanced intratumoral retention of Lipiodol with potential for improved therapeutic efficacy.
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