title: Biocompatible microemulsion modifies the pharmacokinetic profile and cardiotoxicity of doxorubicin.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Sao Paulo State University, UNESP, Araraquara 14801-902, SP, Brazil.
authors.forename: Juliana Uruguay Correa Vidigal
authors.initials: JU
authors.lastname: Assumpção
authors.forename: Michel Leandro
authors.initials: ML
authors.lastname: Campos
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Ferraz Nogueira Filho
authors.forename: Kelly Chrystina
authors.initials: KC
authors.lastname: Pestana
authors.forename: Helen Mariana
authors.initials: HM
authors.lastname: Baldan
authors.forename: Thalita Pedroni
authors.initials: TP
authors.lastname: Formariz Pilon
authors.forename: Anselmoc Gomes
authors.initials: AG
authors.lastname: de Oliveira
authors.forename: Rosângela Gonçalves
authors.initials: RG
authors.lastname: Peccinini
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D052279:Creatine Kinase, MB Form / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D004655:Emulsions; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004655:Emulsions; D008055:Lipids; D004317:Doxorubicin; D052279:Creatine Kinase, MB Form