title: Biocompatible microemulsion modifies the tissue distribution of doxorubicin.
abstract: The incorporation of doxorubicin (DOX) in a microemulsion (DOX-ME) has shown beneficial consequences by reducing the cardiotoxic effects of DOX. The aim of this study was to determine the distribution of DOX-ME in Ehrlich solid tumor (EST) and the heart, and compare it with that of free DOX. The distribution study was conducted with female Swiss mice with EST (n = 7 per group; 20-25 g). Animals received a single dose (10 mg/kg, i.p.) of DOX or DOX-ME 7 days after tumor inoculation. Fifteen minutes after administration, the animals were sacrificed, and the tumor and heart tissues were taken for immediate analysis by ultra-performance liquid chromatography. No difference was observed in DOX concentration in tumor tissue between DOX and DOX-ME administration. However, the most remarkable result in this study was the statistically significant reduction in DOX concentration in heart tissue of animals given DOX-ME. Mean DOX concentration in heart tissue was 0.92 ± 0.54 ng mg(-1) for DOX-ME and 1.85 ± 0.34 ng mg(-1) for free DOX. In conclusion, DOX-ME provides a better tissue distribution profile, with a lower drug concentration in heart tissue but still comparable tumor drug concentration, which indicates that antitumor activity would not be compromised.
authors.affiliation: Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University - UNESP, Araraquara, 14801-902, SP, Brazil.
authors.forename: Caroline Damico
authors.initials: CD
authors.lastname: Candido
authors.forename: Michel Leandro
authors.initials: ML
authors.lastname: Campos
authors.forename: Juliana Uruguay
authors.initials: JU
authors.lastname: Correa Vidigal Assumpção
authors.forename: Kelly Chrystina
authors.initials: KC
authors.lastname: Pestana
authors.forename: Elias Carvalho
authors.initials: EC
authors.lastname: Padilha
authors.forename: Iracilda Zeppone
authors.initials: IZ
authors.lastname: Carlos
authors.forename: Rosângela Gonçalves
authors.initials: RG
authors.lastname: Peccinini
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D002853:Chromatography, Liquid; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004655:Emulsions; D005260:Female; D051379:Mice; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004655:Emulsions; D004317:Doxorubicin
keywords: Ehrlich tumor; UPLC; distribution; doxorubicin; formulation; liquid chromatography; microemulsion; pharmacokinetics; toxicology