Effect of Knockout of Mdr1a and Mdr1b ABCB1 Genes on the Systemic Exposure of a Doxorubicin-Conjugated Block Copolymer in Mice

摘要: We previously elucidated that ATP-binding cassette subfamily B member 1 (ABCB1) mediates the efflux of doxorubicin-conjugated block copolymers from HeLa cells. Here, we investigated role ABCB1 in vivo behavior a polymer Mdr1a/1b(-/-) mice. The area under curve for intravenously administered mice was 2.2-fold greater than wild-type mostly distributed liver followed by spleen and less so brain, heart, kidney, lung. amount excreted urine significantly decreased amounts polymers feces were similar both groups despite higher systemic exposure Confocal microscopy images showed localized CD68(+) macrophages liver. These results show knockout prolonged Our suggest mediated excretion feces. provide valuable information about vivo, which is important evaluating pharmacokinetics active substances conjugated to or accumulation vivo.