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Stable paclitaxel formulations in oily contrast medium
In-Hyun Lee1, Yeong Taek Park, Kyungho Roh
1Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolkok-dong, Sungbuk-ku, Seoul 136-791, Republic of Korea.
Summary
Stable paclitaxel solutions in Lipiodol were developed to treat solid tumors. Adding solvents prevented paclitaxel aggregation, leading to complete tumor eradication and long-term survival in mice.
Area of Science:
- Oncology
- Drug Delivery
- Materials Science
Background:
- Paclitaxel is a chemotherapy drug used for solid tumors.
- Lipiodol is an oily contrast medium.
- Paclitaxel precipitates in Lipiodol over time due to hydrogen bonding.
Purpose of the Study:
- To develop stable paclitaxel/Lipiodol solutions and emulsions for cancer treatment.
- To investigate methods to prevent paclitaxel precipitation in Lipiodol.
- To evaluate the efficacy of stable paclitaxel formulations in preclinical models.
Main Methods:
- Paclitaxel was dissolved in Lipiodol with the addition of miscible solvents to prevent aggregation.
- Stable paclitaxel/Lipiodol solutions and water-in-oil emulsions were characterized for stability, physical properties, and in vitro drug release.
- The efficacy of the stable oily paclitaxel solution was tested in a B16F10 melanoma mouse model.
Main Results:
- Addition of small amounts of miscible solvents completely prevented time-dependent paclitaxel aggregation in Lipiodol.
- Paclitaxel stabilized the water-in-oil emulsion of Lipiodol and Iopamiro.
- In mice with B16F10 melanoma, the stable oily paclitaxel solution eradicated tumors within 2 weeks, with mice surviving over 1 year.
- Control mice showed rapid tumor growth, metastasis, and died within 40 days.
Conclusions:
- Stable paclitaxel/Lipiodol solutions and emulsions can be successfully developed by preventing drug precipitation.
- These stable formulations demonstrate significant anti-tumor efficacy in a preclinical model.
- This approach offers a promising strategy for the treatment of solid tumors like hepatocellular carcinoma.