Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5821118 | International Journal of Pharmaceutics | 2012 | 9 Pages |
Abstract
New technologies are needed to deliver medicines safely and effectively. Polymeric nanoparticulate carriers are one such technology under investigation. We examined the intracellular trafficking of doxorubicin-bound block copolymers quantitatively and by imaging doxorubicin-derived fluorescence using confocal microscopy. The polymers were internalized by endocytosis and distributed in endosomal/lysosomal compartments and the endoplasmic reticulum; unlike free doxorubicin, the polymers were not found in the nucleus. Moreover, the ATP-binding cassette protein B1 (ABCB1) transporter may be involved in the efflux of the polymer from cells. This drug delivery system is attractive because the endogenous transport system is used for the uptake and delivery of the artificial drug carrier to the target as well as for its efflux from cells to medium. Our results show that a drug delivery system strategy targeting this endogenous transport pathway may be useful for affecting specific molecular targets.
Keywords
ECFPMTOCMDR1ABCB1DDSRESHBSSPVDFDOX(PBS)AFMDLSDMEMSDSFBSDulbecco's modified Eagle's mediumEndocytosisEDTAethylenediamine tetraacetic acidenhanced cyan fluorescent proteinEPRTransporterDoxorubicinsodium dodecyl sulfatefetal bovine serumDrug delivery systemendoplasmic reticulumIntracellular traffickingPhosphate-buffered salineHank's balanced salt solutionmicrotubule-organizing centermultidrug resistance 1atomic force microscopyConfocal microscopyEnhanced permeability and retentionDynamic Light ScatteringpolyethyleneglycolPolyvinylidene fluoridePEG
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Authors
Kumiko Sakai-Kato, Keiko Ishikura, Yuki Oshima, Minoru Tada, Takuo Suzuki, Akiko Ishii-Watabe, Teruhide Yamaguchi, Nobuhiro Nishiyama, Kazunori Kataoka, Toru Kawanishi, Haruhiro Okuda,