In vitro characterization of cisplatin-loaded superabsorbent polymer microspheres designed for chemoembolization.
OBJECTIVE
To find appropriate contrast media to load cisplatin into superabsorbent polymer (SAP) and to analyze the absorption and elution kinetics of cisplatin to and from SAP.


METHODS
Three contrast media-ioxaglic acid 320 mg/mL, iohexol 300 mg/mL, and iopamidol 300 mg/mL-were tested for solubility of a new highly soluble cisplatin powder. The appropriate concentrations of cisplatin were predetermined according to the solubility in each contrast medium. For each concentration, we assessed the cisplatin elution kinetics with an atomic absorption spectrophotometer. The SAP particle diameters (106-150 microm dry size) before and after drug elution were also measured.


RESULTS
The concentrations of cisplatin were predetermined as 2.5 mg/mL in ioxaglic acid, 2.5 mg/mL in iohexol, and 5.0 mg/mL in iohexol. At these concentrations, 100 mg of SAP carried 5 mg, 25 mg, and 50 mg of cisplatin dissolved in ioxaglic acid (2.5 mg/mL) and iohexol (2.5 mg/mL and 5.0 mg/mL), respectively. Cisplatin-loaded SAP in ioxaglic acid and iohexol exhibited similar elution profiles, with cisplatin fractions of 15%, 40%, 70%, and 95% at 1, 3, 6, and 24 hours, respectively. By drug elution, the mean particle diameter changed from 0.31 mm to 0.61 mm in ioxaglic acid (2.5 mg/mL), from 0.54 mm to 0.60 mm in iohexol 2.5 mg/mL, and from 0.63 mm to 0.59 mm in iohexol 5.0 mg/mL.


CONCLUSIONS
SAP was confirmed to absorb and elute cisplatin within 24 hours. When mixed with iohexol, SAP carried a ten times larger dose of cisplatin and expanded twice as large as when mixed with ioxaglic acid. Cisplatin-loaded SAP may have potential as a drug delivery system for the clinical treatment of liver tumors.
Maeda
Noboru
N
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan. n-maeda@radiol.med.osaka-u.ac.jp
Osuga
Keigo
K
Higashihara
Hiroki
H
Mikami
Koji
K
Tomoda
Kaname
K
Hori
Shinichi
S
Nakazawa
Tetsuro
T
Nakamura
Hironobu
H
D000042:Absorption; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004621:Embolization, Therapeutic / Q000379:methods*; D006490:Hemostatics / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008863:Microspheres; D011108:Polymers / Q000737:chemistry*
D004337:Drug Carriers; D006490:Hemostatics; D011108:Polymers; D002945:Cisplatin