Cisplatin‐conjugated Gelpart: initial study in vitro

Abstract

In Japan, Gelpart (Nippon Kayaku, Tokyo, Japan) is commercially available as an embolic agent made of gelatin for hepatocellular carcinoma. The object of this study was to develop cisplatin-conjugated Gelpart, confirm its bonding capability and confirm cisplatin-release from it in vitro. Gelpart (80 mg) were immersed in 50 mL of the cisplatin solution (0.3 mg/mL) at 38 degrees C for 1 hour to allow conjugation to cisplatin. Half of them were washed with double distilled water and centrifuged seven times to remove the uncombined cisplatin from Gelpart. Five mg of washed Gelpart and 5 mg unwashed Gelpart were freeze-dried and the platinum concentrations in these Gelpart were analyzed. In an in vitro release test, 30 mg of each cisplatin-conjugated Gelpart were placed in 10 mL of phosphate buffered salts (PBS) containing 0.01 wt.% Tween 80 and the system was shaken reciprocally at 72 strokes/min at 38 degrees C. At different time intervals (1, 3, 6, 12 and 24 hours), 5 mL of the supernatant was pipetted out and immediately after that the same volume of PBS was added. The platinum concentration of the solutions sampled was measured and the release rate from cisplatin-conjugated Gelpart was calculated. The platinum concentrations (microg/g) of unwashed Gelpart and washed Gelpart were, respectively, 9563.5 +/- 101.1 and 6396.5 +/- 14.8. The release rates (%) from unwashed Gelpart and from washed Gelpart were, respectively, 43.1, 56.3, 56.5, 58.5, 60.9 and 5.8, 6.7, 8.5, 11.0, 12.0. Gelpart had a bonding capability to cisplatin and an ability of sustained release from it. Cisplatin-conjugated Gelpart might become a simple embolic agent with drug delivery systems.