油性造影剤を用いた安定なパクリタキセル製剤の開発
This study investigated stable formulations of paclitaxel dissolved in Lipiodol, an oily contrast medium, targeting solid tumors including hepatocellular carcinoma. Paclitaxel dissolved readily in Lipiodol but underwent time-dependent aggregation driven by inter- and intramolecular hydrogen bonding. Addition of small quantities of Lipiodol-miscible co-solvents completely suppressed this aggregation. Paclitaxel was also found to contribute to the stabilization of water-in-oil emulsions composed of Lipiodol and Iopamiro. Physical properties and in vitro release profiles of the resulting solutions and emulsions were characterized. In a B16F10 melanoma model in C57BL/6 mice, animals receiving the stable oily paclitaxel solution showed complete tumor eradication within 2 weeks and survived beyond 1 year, while control animals experienced rapid tumor growth with metastasis and all died within 40 days.
Paclitaxel aggregation in Lipiodol results from inter- and intramolecular hydrogen bonding among paclitaxel molecules; addition of Lipiodol-miscible co-solvents disrupts these interactions, preventing precipitation and maintaining formulation stability.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/15653161