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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastroenterol. Aug 7, 2026; 32(29): 119374
Published online Aug 7, 2026. doi: 10.3748/wjg.119374
Enhancing delivery of doxorubicin using triolein emulsion in rabbit VX2 liver tumor model
Yong-Woo Kim, Hak Jin Kim, Seon Hee Choi, Mi Sook Yun
Yong-Woo Kim, Department of Radiology, Severance Hospital, College of Medicine, Yonsei University, Seoul 03722, South Korea
Yong-Woo Kim, Department of Radiology, Pusan National University Hospital, Pusan National University College of Medicine, Busan 49241, South Korea
Hak Jin Kim, Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University College of Medicine, Busan 49241, South Korea
Seon Hee Choi, Department of Radiology, Pusan National University, Busan 49241, South Korea
Mi Sook Yun, Department of Biostatistics, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan-si 50612, Gyeonggi-do, South Korea
Author contributions: Kim YW and Kim HJ contributed to conceptualization, writing original draft preparation, writing, review and editing, writing revision review and editing, visualization and supervision; Yun MS contributed to statistical analysis; Kim YW, Kim HJ, and Yun MS contributed to analyzed the data; Kim YW, Choi SH, and Yun MS contributed to data curation; Kim YW contributed to writing revision draft preparation; Kim YW and Choi SH contributed to performed experiments.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the (approval No. PNUYH-2019-073).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data presented in the study are available upon request from the corresponding author (hakjink@pusan.ac.kr).
Corresponding author: Hak Jin Kim, PhD, Professor, Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University College of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, South Korea. hakjink@pusan.ac.kr
Received: January 27, 2026
Revised: February 13, 2026
Accepted: March 26, 2026
Published online: August 7, 2026
Processing time: 172 Days and 0.8 Hours
Abstract
BACKGROUND

A previous study reported that a triolein emulsion (TE) injection to the liver markedly enhanced the concentration of doxorubicin by near two-fold. Hence, a TE injection could serve as a beneficial supplementary treatment to enhance the chemotherapeutic efficacy in liver cancer.

AIM

To evaluate the antitumor effects of doxorubicin with and without a TE infusion to the liver in the VX2 hepatic tumor model of rabbit.

METHODS

VX2 tumor tissues were inoculated into the liver of 16 rabbits. Seventeen days after implantation, contrast-enhanced computed tomography (CECT) was performed to localize the hepatic tumors. The rabbits were divided into two groups: TE with doxorubicin (TE-Doxo) (n = 8) and normal saline (NS) with doxorubicin (NS-Doxo) (n = 6). Intra-arterial transcatheter administration was performed via the transauricular approach. Two rabbits in the group without TE failed to undergo the transauricular approach. Follow-up CECT was performed nine days after transcatheter arterial chemoembolization (TACE). The tumor volumes were measured on the pre- and post-TACE CT scans, and the growth ratio was estimated. Statistical analysis was performed (nonparametric Mann-Whitney U tests and the Wilcoxon signed-rank test).

RESULTS

The mean tumor volume was significantly smaller in the TE-Doxo group (from 1913.09 ± 489.58 mm3 to 1229.75 ± 395.61 mm3) than in the NS-Doxo group (from 874.36 ± 361.65 mm3 to 1574.17 ± 890.12 mm3). The mass growth ratio was also significantly reduced in the TE-Doxo group (-41.68% ± 7.32%) than in the NS-Doxo group (76.59% ± 77%; P = 0.002).

CONCLUSION

The TE infusion enhanced the antitumor efficacy of doxorubicin, significantly reducing the tumor volume and growth ratio in the VX2 hepatic tumor model. These results suggest that a TE infusion may be an effective adjuvant treatment to improve the TACE outcomes in hepatic tumor.

Keywords: Transcatheter arterial chemoembolization; Hepatocellular carcinoma; VX2 tumor; Liver; Doxorubicin; Triolein emulsion

Core Tip: The infusion of triolein emulsion into the hepatic arteries increased the liver vascular permeability in the sinusoidal capillaries by transiently disrupting endothelial barriers, leading to a minimal transient decrease in liver function without specific histopathological changes in the rabbit livers. Consequently, any triolein-induced endothelial loosening can substantially enhance drug extravasation into liver tissue. This study aimed to evaluate the antitumor effects of doxorubicin by comparing the changes in tumor volume and the growth ratios between the triolein emulsion with doxorubicin and normal saline with doxorubicin groups via a hepatic arterial infusion in a rabbit liver VX2 tumor model.

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