alexa Nanoemulsion preparations of the anticancer drug dacarbazine significantly increase its efficacy in a xenograft mouse melanoma model.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Tagne JB, Kakumanu S, Nicolosi RJ

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Abstract 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. This article was published in Mol Pharm and referenced in Journal of Nanomedicine & Nanotechnology

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