Frontiers in pharmacology · 2026
Sequential and synergistic delivery of lipiodol and drug-eluting microspheres circumvents incompatibility to enhance targeted chemoembolization.
СтатьяНазвание и аннотация: Перевод в очереди
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Du Nan, Zhang Wen, Chen Chao, Wang Ying, He Xinhong, Luo Jianjun, Yan Zhiping, Li Wen-Tao
Аннотация
BACKGROUND: Conventional (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.
METHODS: Animals 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.
RESULTS: The 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).
CONCLUSION: The 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.
METHODS: Animals 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.
RESULTS: The 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).
CONCLUSION: The 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.