Efficacy of BCNU and paclitaxel loaded subcutaneous implants in the interstitial chemotherapy of U-87 MG human glioblastoma xenografts.
Nude mice were challenged with human U-87 MG glioblastoma tumors to assess the efficacy of different cytostatics and different application protocols. While the intraperitoneal application of BCNU solutions (3 times 20 mg BCNU/kg) had no effect on tumor growth, the application of polymer matrices made of a physical mixture of poly(1,3-bis[carboxyphenoxpropane]-co-sebacic acid) 20:80 with poly(D,L-lactic-co-glycolic acid) loaded with 0.25 mg BCNU, slowed down the growth of tumors significantly. When the animals were treated with implants carrying 0.25 mg BCNU they responded to the treatment whether the tumor had been inoculated recently (9 days ago) or whether it was fully established (after 20 days). After its sensitivity was proven, the xenograft model was used to further investigate the efficacy of anticancer drugs and some treatment regimens using polymer implants. Thus the tumor model allowed to discriminate between the efficacy of different doses of BCNU. Only implants loaded with 0.75 or 1 mg of BCNU led to a substantial suppression of tumor growth over approximately 2 months. While BCNU was only able to suppress the growth of the tumor, the combination of BCNU with paclitaxel led to a complete remission in some animals. These preliminary results suggest that combinations of cytostatics might improve local chemotherapy of malignant glioma substantially. Based on our data it will be worthwhile to investigate implants that release drugs such as BCNU and paclitaxel closer. Amongst other factors we will try to elucidate the effect of repetitive doses of drugs using programmable implants.
Vogelhuber
W
W
Department of Pharmaceutical Technology, University of Regensburg, 93040, Regensburg, Germany.
Spruss
T
T
Bernhardt
G
G
Buschauer
A
A
Göpferich
A
A
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005079:Excipients; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D011108:Polymers
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D004343:Drug Implants; D005079:Excipients; D011108:Polymers; D017239:Paclitaxel; D002330:Carmustine