Cisplatin incorporated in microspheres: development and fundamental studies for its clinical application.
A new drug delivery formulation, biodegradable glycolic acid-lactic acid copolymer (PGLA) microspheres incorporating cisplatin (CDDP-MS) has been developed for the treatment of peritoneal carcinomatosis. Scanning electron microscopy showed that CDDP-MS has a smooth surface and few cisplatin crystals in the hollow. An electron probe micro analyzer revealed that cisplatin was located mainly in the matrix in the state of a molecule. Release profile in vitro of CDDP from microspheres showed that the initial burst was 21.2% and the remaining CDDP was released slowly thenceforth over 14 days. Hydrolysis of CDDP-MS progresses very slowly during the 14 days, but there was no morphological change in the SEM views. The dimethylformamide content entrapped within CDDP-MS, determined by a gas chromatography, was 136 ppm at the evaporation temperature of 47 degrees C. The 50% lethal dose value of CDDP-MS, calculated by the Litchfield-Wilcoxon method, was reduced to 57% of the cisplatin solution. Therapeutic experiment on mice with peritoneal carcinomatosis showed that CDDP-MS did not enhance therapeutic effect as compared with the same dose dosage of a cisplatin aqueous solution but large quantities of cisplatin could be given in case of CDDP-MS owing to less toxicity.
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. fujiyama@koto.kpu-m.ac.jp
Junshin
J
Fujiyama
Yuen
Y
Nakase
Kimihiko
K
Osaki
Chouhei
C
Sakakura
Hisakazu
H
Yamagishi
Akeo
A
Hagiwara
D000818:Animals; D002945:Cisplatin / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008863:Microspheres; D013678:Technology, Pharmaceutical / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D002945:Cisplatin