Nanoemulsion preparations of the anticancer drug dacarbazine significantly increase its efficacy in a xenograft mouse melanoma model.
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.
Tagne
Jean-Bosco
JB
Center for Health and Disease Research, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
Kakumanu
Srikanth
S
Nicolosi
Robert J
RJ
D000328:Adult; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003606:Dacarbazine / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; D004337:Drug Carriers; D004655:Emulsions; D003606:Dacarbazine