Pharmaceutical research · 2014
Pharmacokinetics, antitumor and cardioprotective effects of liposome-encapsulated phenylaminoethyl selenide in human prostate cancer rodent models.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kang Jeong Yeon, Eggert Mathew, Mouli Shravanthi, Aljuffali Ibrahim, Fu Xiaoyu, Nie Ben, Sheil Amy, Waddey Kendall, Oldham Charlie D, May Sheldon W, Amin Rajesh, Arnold Robert D
Аннотация
PURPOSE: Cardiotoxicity associated with the use of doxorubicin (DOX), and other chemotherapeutics, limits their clinical potential. This study determined the pharmacokinetics and antitumor and cardioprotective activity of free and liposome encapsulated phenyl-2-aminoethyl-selenide (PAESe).
METHODS: The pharmacokinetics of free PAESe and PAESe encapsulated in liposomes (SSL-PAESe) were determined in rats using liquid chromatography tandem mass-spectrometry. The antitumor and cardioprotective effects were determined in a mouse xenograft model of human prostate (PC-3) cancer and cardiomyocytes (H9C2).
RESULTS: The encapsulation of PAESe in liposomes increased the circulation half-life and area under the drug concentration time profile, and decreased total systemic clearance significantly compared to free PAESe. Free- and SSL-PAESe improved survival, decreased weight-loss and prevented cardiac hypertrophy significantly in tumor bearing and healthy mice following treatment with DOX at 5 and 12.5 mg/kg. In vitro studies revealed PAESe treatment altered formation of reactive oxygen species (ROS), cardiac hypertrophy and gene expression, i.e., atrial natriuretic peptide and myosin heavy chain complex beta, in H9C2 cells.
CONCLUSIONS: Treatment with free and SSL-PAESe exhibited antitumor activity in a prostate xenograft model and mitigated DOX-mediated cardiotoxicity.
METHODS: The pharmacokinetics of free PAESe and PAESe encapsulated in liposomes (SSL-PAESe) were determined in rats using liquid chromatography tandem mass-spectrometry. The antitumor and cardioprotective effects were determined in a mouse xenograft model of human prostate (PC-3) cancer and cardiomyocytes (H9C2).
RESULTS: The encapsulation of PAESe in liposomes increased the circulation half-life and area under the drug concentration time profile, and decreased total systemic clearance significantly compared to free PAESe. Free- and SSL-PAESe improved survival, decreased weight-loss and prevented cardiac hypertrophy significantly in tumor bearing and healthy mice following treatment with DOX at 5 and 12.5 mg/kg. In vitro studies revealed PAESe treatment altered formation of reactive oxygen species (ROS), cardiac hypertrophy and gene expression, i.e., atrial natriuretic peptide and myosin heavy chain complex beta, in H9C2 cells.
CONCLUSIONS: Treatment with free and SSL-PAESe exhibited antitumor activity in a prostate xenograft model and mitigated DOX-mediated cardiotoxicity.
Предметные рубрики MeSH
AnimalsAntineoplastic AgentsAntioxidantsArea Under CurveCardiomegalyCell Line, TumorChemistry, PharmaceuticalChromatography, LiquidDisease Models, AnimalDose-Response Relationship, DrugDoxorubicinEthylaminesGene Expression RegulationHalf-LifeHumansInjections, IntravenousLiposomesMaleMass SpectrometryMetabolic Clearance RateMice, NudeMyocytes, CardiacOrganoselenium CompoundsOxidative StressProstatic NeoplasmsRats, Inbred F344Reactive Oxygen SpeciesTechnology, PharmaceuticalTumor BurdenXenograft Model Antitumor Assays