Evaluation of in vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer against 9L gliosarcoma

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 59; no. 1; pp. 169 - 175
• Main Authors: Lee, Jin Soo, An, Tae Kun, Chae, Gang Soo, Jeong, Je Kyo, Cho, Sun Hang, Lee, Hai Bang, Khang, Gilson
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 2005
• Subjects: 9L gliosarcoma; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antitumor activity; BCNU; Carmustine - administration & dosage; Carmustine - pharmacokinetics; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Drug Evaluation, Preclinical - methods; Gliosarcoma - drug therapy; Gliosarcoma - metabolism; Lactic Acid - administration & dosage; Lactic Acid - pharmacokinetics; Male; Malignant gliomas; PLGA wafer; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - pharmacokinetics; Polymers - administration & dosage; Polymers - pharmacokinetics; Rats; Rats, Inbred F344; Antitumor activity; Malignant gliomas; 9L gliosarcoma; PLGA wafer; BCNU
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2004.06.006

The purpose of the present study was to develop implantable BCNU-loaded poly( d, l-lactide-co-glycolide) (PLGA) wafer for the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and to evaluate its in vitro and in vivo antitumor activity. The release rate of BCNU from PLGA wafer increased with the increase of BCNU amount loaded and the release was continued until 7 days. In vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer was investigated using in vitro cytotoxicity against 9L gliosarcoma cells and a subcutaneous (s.c.) solid tumor model of 9L gliosarcoma, respectively. The wafers containing BCNU showed more effective cytotoxicity than BCNU powder due to its short half-life and inhibited the proliferation of 9L gliosarcoma cells. BCNU-loaded PLGA wafer delayed the growth of the tumors significantly and increasing the dose of BCNU in the wafer resulted in a substantial regression of the tumor. These results of antitumor activity of BCNU-loaded PLGA wafer demonstrate the feasibility of the wafers for clinical application.