Injectable intratumoral hydrogel as 5-fluorouracil drug depot.
The effectiveness of systemically administered anticancer treatments is limited by difficulties in achieving therapeutic doses within tumors, a problem that is complicated by dose-limiting side effects to normal tissue. To increase the efficacy and reduce the toxicity of systemically administered anticancer 5-fluorouracil (5-Fu) treatments in patients, intratumoral administration of an injectable hydrogel has been evaluated in the current work. The MPEG-b-(PCL-ran-PLLA) diblock copolymer (MCL) containing 5-Fu existed in an emulsion-sol state at room temperature and rapidly gelled in vivo at the body temperature. MCL acted as in vivo biodegradable drug depot over a defined experimental period. A single injection of 5-Fu-loaded MCL solution resulted in significant suppression of tumor growth, compared with repeated injection of free 5-Fu as well as saline and MCL alone. For both repeated injections of free 5-Fu and single injection of 5-Fu-loaded MCL, most of the 5-Fu was found in the tumor, indicating the maintenance of therapeutic concentrations of 5-Fu within the target tumor tissue and the prevention of systemic toxicity associated with 5-Fu in healthy normal tissues. In conclusion, this work demonstrated that intratumoral injection of 5-Fu-loaded MCL may induce significant suppression of tumor growth through effective accumulation of 5-Fu in the tumor.
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Republic of Korea.
Hyo Won
HW
Seo
Da Yeon
DY
Kim
Doo Yeon
DY
Kwon
Jin Seon
JS
Kwon
Ling Mei
LM
Jin
Bong
B
Lee
Jae Ho
JH
Kim
Byoung Hyun
BH
Min
Moon Suk
MS
Kim
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D020100:Hydrogels / Q000737:chemistry*; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D014783:Viscosity
D000964:Antimetabolites, Antineoplastic; D001672:Biocompatible Materials; D020100:Hydrogels; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D005472:Fluorouracil