Application of Idarubicin loaded Equalspheres in the TACE procedure for Rabbit Liver Tumor Model.

Abstract

RATIONALE AND OBJECTIVES: To investigate the in vitro drug loading and release effects of uniformly sized beads Equalspheres (ES) for idarubicin (IDA) and its application in rabbit liver VX₂ tumor model. MATERIAL AND METHODS: The ES sizes of 70 µm and 100 µm were divided into three groups according to different IDA and ES ratios and different IDA concentrations for the drug loading experiment. The optimal concentration group was selected for the drug release experiment. The diameter and Zeta potential of the ES was measured, and the shrinkage rate was calculated. The rabbit liver VX₂ tumor model was divided into a control group, a TACE group, and an IDA-TACE group. The HE and IHC staining data were compared and analyzed. RESULTS: The shrinkage of 70 and 100 µm ES with IDA loaded exceeds 20%. Both 70 µm and 100 µm ES can rapidly load IDA, and ES's loading efficiency with 10mg/ml IDA is higher than that with 5mg/ml. The encapsulation rate of 70 µm ES with IDA concentrations of 10mg/ml and 5mg/ml after 5 min of drug administration were (90.75±3.57)% and (83.97±2.34)%, respectively. The encapsulation rates of 100 µm ES with IDA concentrations of 10mg/ml and 5mg/ml after 5 min of drug administration were (93.66±2.19)% and (89.92±1.52)%, respectively. The 1 h and 24 h release rates of 70 µm ES were (62.64±1.88)% and (88.77±7.27)%, respectively. The 1 h and 24 h release rates of 100 µm ES were (80.74±4.90)% and (96.42±9.48)%, respectively. The 70 µm ES was chosen to perform TACE and IDA-TACE. Pathological results suggested that the expression of PCNA in the tumor after IDA-TACE was significantly downregulated, while the expression of VEGF, CD31, and HIF-1 was increased after embolization in 1w and significantly decreased in 2w. CONCLUSION: This study demonstrated that ES can rapidly load IDA and achieve sustained release. The shrinkage of ES needs to be a concern in clinical applications. The IDA-TACE is an effective procedure for achieving hepatic tumor locoregional treatment.