Efficacy of an MPC-BMA co-polymer as a nanotransporter for paclitaxel.
BACKGROUND
Paclitaxel (PTX) is administered as a solution in polyoxyethylated castor oil (CO) due to its low water solubility, but solvent-induced side-effects may be severe.


METHODS
PMB30W is a co-polymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and butyl methacrylate (BMA). Cytotoxicities of PTX in PMB30W (PTX-PMB30W) were examined in cell culture and in vivo.


RESULTS
PTX-PMB30W and PTX in dimethyl sulfoxide showed similar toxicity in breast cancer cell lines MCF-7, SK-BR-3 and MX-1. Antitumor efficacies of PTX-PMB30W and PTX in CO (PTX-CO) were similar following weekly intraperitoneal administration of 50 mg/kg PTX in nude mice transplanted with MX-1 cells. At 200 mg/kg PTX, all animals died within 1 minute of PTX-CO administration. However, all animals receiving PTX-PBM30W survived. Ulceration occurred following subcutaneous injection of PTX-CO, but injection of PTX-PMB30W did not cause skin changes.


CONCLUSIONS
Our data suggest that PMB30W can act as an effective PTX nanotransporter.
Wada
Masahiro
M
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Jinno
Hiromitsu
H
Ueda
Masakazu
M
Ikeda
Tadashi
T
Kitajima
Masaki
M
Konno
Tomohiro
T
Watanabe
Junji
J
Ishihara
Kazuhiko
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D005260:Female; D006801:Humans; D008689:Methacrylates / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012883:Skin Ulcer / Q000139:chemically induced / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008689:Methacrylates; D053769:Nanocapsules; D010767:Phosphorylcholine; C079200:poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate); D017239:Paclitaxel; D004121:Dimethyl Sulfoxide