Evaluation of the role of cisplatin-conjugated-soluble gelatin sponge: feasibility study in a swine model.
OBJECTIVE
To evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model.


METHODS
Fifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediately after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio.


RESULTS
Sequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC(0-30), AUC(30-120), and AUC(120-420) were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67%, p = 0.014).


CONCLUSIONS
Cisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage.
Department of Radiology, Wakayama Medical University, 811-1 Kimiidera, Wakayamashi, Wakayama, 641-8510, Japan.
Akira
A
Ikoma
Nobuyuki
N
Kawai
Morio
M
Sato
Hiroyuki
H
Minamiguchi
Kouhei
K
Nakata
Motoki
M
Nakai
Hiroki
H
Sanda
Tetsuo
T
Sonomura
Yoshitaka
Y
Kanayama
Yasuo
Y
Sakai
D000792:Angiography / Q000379:methods; D000818:Animals; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005240:Feasibility Studies; D005781:Gelatin Sponge, Absorbable / Q000494:pharmacology*; D006499:Hepatic Artery / Q000000981:diagnostic imaging; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000628:therapy; D008297:Male; D011897:Random Allocation; D012016:Reference Values; D012307:Risk Factors; D012380:Role; D012680:Sensitivity and Specificity; D012995:Solubility; D013552:Swine
D004337:Drug Carriers; D002945:Cisplatin