Supplementary file 2_Sequential and synergistic delivery of lipiodol and drug-eluting microspheres circumvents incompatibility to enhance targeted chemoembolization.docx

BackgroundConventional (cTACE) and drug-eluting bead transarterial chemoembolization (D-TACE) are limited by physicochemical incompatibility when lipiodol and microspheres are mixed. This study evaluated a sequential co-delivery strategy (M-TACE) designed to synergize these agents in a rabbit VX2 liver tumor model.
MethodsAnimals were randomized into control, cTACE, D-TACE, and M-TACE (epirubicin-lipiodol emulsion followed by epirubicin-loaded microspheres) groups. Primary outcomes included pharmacokinetics, tumor necrosis, and lipiodol distribution.
ResultsThe cTACE group showed a higher systemic peak epirubicin concentration (C ∼ max∼: 276.08 ± 41.74 ng/mL) than D-TACE (79.37 ± 16.26 ng/mL) and M-TACE (92.13 ± 12.68 ng/mL) (p < 0.001), while total 24-h exposure (AUC0–24 h) was comparable. M-TACE achieved intratumoral drug concentrations equivalent to D-TACE at day 1 and 14, confirming unimpaired microsphere elution. M-TACE induced superior tumor necrosis (95.4% ± 6.7%) versus cTACE (85.1% ± 6.2%) and D-TACE (88.6% ± 8.4%) (p < 0.001), with less peritumoral liver necrosis than D-TACE (50.9% ± 6.0% vs. 61.7% ± 9.0%, p = 0.039). M-TACE also yielded more focal lipiodol deposition (72.2% ± 7.4% tumor coverage) with reduced parenchymal extravasation versus cTACE (92.9% ± 7.8%; p < 0.001).
ConclusionThe sequential M-TACE strategy successfully decouples lipiodol and microsphere delivery, circumvents the practical consequences of incompatibility while harnessing synergistic advantages—lipiodol’s capillary blockade and microspheres’ sustained drug release—resulting in enhanced efficacy and favorable local safety profile.