title: Combination antitumor effects of micelle-loaded anticancer drugs in a CT-26 murine colorectal carcinoma model.
abstract: Experiments were designed to evaluate the in vitro cytotoxic interactions of anticancer drugs in combination, evaluate synergistic activity in vivo and utilize micelle-forming polymeric drugs as drug carriers in a murine cancer model. Antitumor effects of 5-fluorouracil, cisplatin, CPT-11, oxaliplatin, etoposide, mitomycin-C, doxorubicin and paclitaxel were evaluated by determination of in vitro cytotoxicity to CT-26 colorectal tumor cells or in vivo following a subcutaneous transplant in BALB/c mice. Single agent and combination in vivo studies were also performed using drug-loaded polymeric micelles composed of poly(gamma-benzyl L-glutamate) and poly(ethylene oxide) (GEG) or poly(L-lactide)/poly(ethylene glycol) (LE) diblock copolymer. After 3 days exposure, the mean IC(50) (microg/mL) for 5-fluorouracil, cisplatin, CPT-11, oxaliplatin, etoposide, mitomycin-C, doxorubicin and paclitaxel were 0.95, 2.01, 4.47, 3.34, 3.5, 1.96, 1.8 and 2.1, respectively. When tumor cells were exposed to doxorubicin concurrently with etoposide or paclitaxel, evidence of synergy was observed in CT-26 cells in vitro. Doxorubicin and paclitaxel loaded into GEG or LE copolymers at a high concentration (19.5 and 16.7 wt%, respectively) were almost completely released (83.2% and 93.7%, respectively) by day 3. When tumor-bearing mice were treated in combination with doxorubicin-paclitaxel or doxorubicin-etoposide, substantial antitumor activity was evident compared with single therapy. These data suggest that in vitro cytotoxicity of anticancer drugs is related to in vivo results, and chemotherapy using micelle-loaded anticancer drugs represents a promising potential as a carrier system in modulating drug delivery.
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: Hee Sam
authors.initials: HS
authors.lastname: Na
authors.forename: Yeun Keun
authors.initials: YK
authors.lastname: Lim
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Lim
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kang
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D015996:Survival Rate / Q000639:trends
chemical_list: D008823:Micelles