In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine-iodide (TMP) in liposomes for the treatment of angiogenesis and metastasis.

Abstract

Phytosphingosine and methyl derivatives are important mediators on cellular processes, and are associated with cell growth and death. The antitumor activity of N,N,N-trimethylphytosphingosine-iodide (TMP) as a novel potent inhibitor of angiogenesis and metastasis was evaluated in B16F10 murine melanoma cells. The results indicated that TMP itself effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors as well as in vivo lung metastasis. However, TMP slightly suppressed in vivo experimental tumor metastasis in its free form and induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP, a liposomal formulation was prepared and tested for its effectiveness. TMP liposomes retained the effectiveness of TMP in vitro while side effects were reduced, and both in vivo experimental and spontaneous tumor metastasis were significantly suppressed. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis as well as in vivo metastasis, and a liposomal formulation is more efficient delivery system for TMP treatment than solution.

• Authors: Chung Kil Song, Ju-Hee Lee, Alexander Jahn, Myeong Jun Choi, Sung Keon Namgoong, Soon-Sun Hong, Saeho Chong, Chang-Koo Shim, Suk-Jae Chung, Dae-Duk Kim
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 434 Issue 1-2 Pg. 191-8 (Sep 15 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 22643227 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Liposomes
• N,N,N-trimethylphytosphingosine
• Quaternary Ammonium Compounds
• Sphingosine

Topics

• Angiogenesis Inhibitors (administration & dosage, pharmacology, toxicity)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, toxicity)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Hemolysis (drug effects)
• Humans
• Liposomes
• Lung Neoplasms (drug therapy, pathology)
• Melanoma, Experimental (blood supply, drug therapy, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis
• Neovascularization, Pathologic (drug therapy, pathology)
• Quaternary Ammonium Compounds (administration & dosage, pharmacology, toxicity)
• Rats
• Sphingosine (administration & dosage, analogs & derivatives, pharmacology, toxicity)