Antitumor Effects of Doxorubicin-Loaded Cellulose Nanoparticles in the Rabbit VX2 Liver Tumor Model.

Abstract

PURPOSE: To evaluate the preclinical efficacy and safety of transarterial chemoembolization (TACE) using doxorubicin-loaded biocompatible cellulose nanoparticles in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: Following institutional animal care committee approval, 23 rabbits with VX2 liver tumors were randomized into three groups: Group A (n&#x2009;=&#x2009;9) received doxorubicin-loaded cellulose nanoparticles with ethiodized oil; Group B (n&#x2009;=&#x2009;9) received doxorubicin with ethiodized oil; and Group C (n&#x2009;=&#x2009;5) served as untreated controls. Tumor size was monitored via ultrasound for 4&#xa0;weeks, and serum liver enzymes (aspartate transaminase and alanine transaminase) were measured on days 1, 3, and 7 to assess hepatotoxicity. An additional 10 healthy rabbits were randomized into two groups: Group D (n&#x2009;=&#x2009;5) received doxorubicin-loaded cellulose nanoparticles with ethiodized oil, and Group E (n&#x2009;=&#x2009;5) received doxorubicin with ethiodized oil, to measure serum doxorubicin concentrations up to 30&#xa0;min post-treatment. RESULTS: Group A demonstrated significantly slower overall tumor growth compared to Group C (p&#x2009;=&#x2009;0.005) and slower growth between days 24 and 27 compared to Group B (p&#x2009;=&#x2009;0.037). Pharmacokinetic analysis showed significantly lower serum doxorubicin levels in Group D than Group E at 2 and 5&#xa0;min post-delivery (p&#x2009;<&#x2009;0.05). Hepatotoxicity peaked at 24&#xa0;h, with significantly lower alanine transaminase levels in Group A compared to Group B (p&#x2009;=&#x2009;0.025), normalizing by day 7. CONCLUSION: TACE using doxorubicin-loaded cellulose nanoparticles demonstrated promising preclinical efficacy and safety compared to conventional TACE. LEVEL OF EVIDENCE: No level of evidence, Animal Study.