Stable paclitaxel formulations in oily contrast medium.
Stable paclitaxel/Lipiodol solutions as well as emulsions were developed for the treatment of solid tumors including hepatocellular carcinoma. Paclitaxel could be dissolved in Lipiodol, an oily contrast medium, but precipitated out and formed aggregates with time. Paclitaxel precipitation was due to the inter- and intra-molecular hydrogen bonding of paclitaxel molecules. Time-dependent paclitaxel aggregation was completely prevented by adding small amounts of additional solvents, which are miscible with Lipiodol. It was also notable that paclitaxel helped in stabilizing the water-in-oil (w/o) type emulsion of Lipiodol and Iopamiro. The stability, physical properties and in vitro drug release profiles of the stable paclitaxel solutions and emulsions were characterized. When the stable oily paclitaxel solution was used for the treatment of B16F10 melanoma in C57BL/6 mice, the malignant cells were eradicated completely in 2 weeks, whereas the solid tumor grew rapidly and metastasized to the thigh and to other organs in the control group. Also, the mice survived for more than 1 year after the paclitaxel treatment, whereas all of those in the control group died in 40 days.
Lee
In-Hyun
IH
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolkok-dong, Sungbuk-ku, Seoul 136-791, Republic of Korea.
Park
Yeong Taek
YT
Roh
Kyungho
K
Chung
Hesson
H
Kwon
Ick Chan
IC
Jeong
Seo Young
SY
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003287:Contrast Media / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D007459:Iodized Oil; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy; D009821:Oils; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012995:Solubility; D012997:Solvents
D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D004655:Emulsions; D009821:Oils; D012997:Solvents; D007459:Iodized Oil; D004317:Doxorubicin; D017239:Paclitaxel