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.
Subject(s)
Antibiotics, Antineoplastic/pharmacokinetics , Biocompatible Materials , Doxorubicin/pharmacokinetics , Emulsions , Animals , Chromatography, Liquid , Female , Mice , Tissue DistributionABSTRACT
Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. However, the clinical use of DOX is limited because of its cardiotoxicity, a dose-dependent effect. Colloidal drug delivery systems, such as microemulsions (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a new DOX ME (DOX-ME). The PK profile of DOX-ME was determined and compared with that of the conventional DOX after single-dose administration (6 mg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in both animal groups before and after drug administration. The plasma DOX measurements were performed by high-performance liquid chromatography with fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest® kit. The ME system showed a significant increase in plasma DOX concentrations and lower distribution volume when compared with conventional DOX. Serum CKMB activity increased after conventional DOX administration but was unchanged in the DOX-ME group. These results demonstrate modifications in drug access to susceptible sites using DOX-ME. DOX-ME displayed features that make it a promising system for future therapeutic application.
