Nanoemulsion Preparations of the Anticancer Drug Dacarbazine Significantly Increase Its Efficacy in a Xenograft Mouse Melanoma Model

作者：Tagne Jean Bosco; Kakurnanu Srikanth; Nicolosi Robert J^*

来源：Molecular Pharmaceutics, 2008, 5(6): 1055-1063.

DOI：10.1021/mp8000556

• Nanoemulsion
• xenograft
• melanoma
• Dacarbazine
• cancer

This article reports on the preparation of a water-soluble nanoemulsion of the highly lipid-soluble drug Dacarbazine (DAC). In addition, relative to suspensions of DAC, the nanoemulsion preparation demonstrated a lower zeta-potential (decreased negative charge, less anionic and more cationic) which has previously been associated with influencing drug membrane permeability. This study also reports that, relative to suspensions of DAC with a mean particle size of 5470 nm, nanoemulsions of DAC having mean particle sizes of 131 nm were more efficacious. For example, in a mouse xenograft model using a human melanoma cell line, a topical application of nanoemulsions of DAC compared to the suspension preparation of DAC produced up to 10-fold greater percent (%) reductions of tumor size. The reduction in tumor size by the intramuscular (IM) injection (-61%) and topical application of the nanoemulsion preparations of DAC (-49%) appeared to be comparable in efficacy, although the former was statistically greater (p < 0.05). In addition, 12 weeks after DAC treatment cessation, 98% of the animals given the IM application of the nanoemulsion of DAC remained tumor-free compared to the control or untreated animals. During this drug cessation period, and compared to the suspension preparations, nanoemulsions of DAC showed 5-fold greater efficacies (73% versus 14%) in preventing tumor growth. In conclusion, in this xenograft mouse model of melanoma, nanoemulsion suspensions of DAC are more efficacious in the treatment and prevention of tumor growth.

• 出版日期2008-12