Enhancement of therapeutic efficacy of bleomycin by incorporation into biodegradable poly-d,l-lactic acid.
A new system for the delivery bleomycin (BLM) to target lesions was established by incorporating BLM into a small cylinder of a biodegradable polylactic acid (PLA) of low molecular weight. Cross-sectional analysis of the system (BLM-PLA) showed that BLM particles were uniformly enclosed in the PLA matrix. In vitro studies demonstrated that BLM was released continuously for more than 3 weeks from BLM-PLA immersed in saline. BLM-PLA was implanted subcutaneously into the backs of rats. A high concentration of BLM was maintained in the connective tissues near the implants for 2 weeks. In contrast, the level of BLM activity was low when a BLM solution (BLM-SOL) was administered subcutaneously by injection. The concentration of BLM in the abdominal lymph nodes was significantly higher following BLM-PLA implantation than following subcutaneous BLM-SOL injection. The inhibitory effects of BLM-PLA and BLM-SOL on tumor growth were compared with no treatment using a subcutaneously transplanted Yoshida sarcoma. The antitumor effect of BLM-PLA was significantly higher than that of BLM-SOL and no treatment. BLM-PLA also resulted in a more favorable distribution of BLM than BLM-SOL. Thus, BLM-PLA proved to be effective in controlling this experimentally transplanted tumor.
Kumanohoso
T
T
First Department of Surgery, Kagoshima University School of Medicine, Sakuragaoka, Japan.
Natsugoe
S
S
Shimada
M
M
Aikou
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism; D001673:Biodegradation, Environmental; D001761:Bleomycin / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems; D004343:Drug Implants; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy
D000903:Antibiotics, Antineoplastic; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D001761:Bleomycin; D019344:Lactic Acid; C033616:poly(lactide)