Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against intraarterial injection of epirubicin.
OBJECTIVE
We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.


METHODS
Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with 1 mg of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI 1.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.


RESULTS
Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.


CONCLUSIONS
It was demonstrated that EPI-PLA, a chemoembolizing material, maintained high local concentrations of the anticancer drug, while maintaining low blood levels of the anticancer drug.
Fujiwara
K
K
Department of Radiology, Kyoto University Hospital, Sakyo-ku, Kyoto-shi 606-8507, Japan.
Hayakawa
K
K
Nagata
Y
Y
Hiraoka
M
M
Nakamura
T
T
Shimizu
Y
Y
Ikada
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D004347:Drug Interactions; D004621:Embolization, Therapeutic / Q000379:methods*; D015251:Epirubicin / Q000008:administration & dosage*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology*; D011817:Rabbits; D012016:Reference Values; D012077:Renal Artery / Q000187:drug effects; D012680:Sensitivity and Specificity
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D015251:Epirubicin; C033616:poly(lactide)