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• W1967778052 endingPage "10" @default.
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• W1967778052 abstract "Clinical applications of first-generation multidrug resistance (MDR) modulators, such as cyclosporin A (CsA) have been hampered because of their severe side effects in vivo. Recent investigations have led to the development of a more potent and less toxic modulator, PSC 833, which is a nonimmunosuppressive analogue of CsA. However, adverse pharmacokinetic interactions between anticancer drugs and PSC 833 have resulted in increased toxicity as compared to the individual toxicity. Our study evaluated the MDR reversing effect of PSC 833 in free, liposomal or Intralipid formulations on the uptake and transport of epirubicin in Caco-2 cells and everted gut sacs of rats. The results showed that PSC 833 in free or liposomal formulations significantly enhanced the intracellular accumulation of epirubicin in a dose-related manner in Caco-2 cells. The optimum in enhancement was observed at the concentration of 2 microM PSC 833. These formulations markedly increased the apical to basolateral absorption of epirubicin in Caco-2 cells and substantially improved the mucosal to serosal absorption of epirubicin in rat jejunum and ileum. PSC 833 in free, liposomal or Intralipid formulations all significantly reduced basolateral to apical efflux of epirubicin across Caco-2 monolayers. However, PSC 833 in liposomes showed greater enhancement than other formulations. In conclusion, PSC 833 and PSC 833 liposomes have the function as MDR reversing agents for the inhibition of intestinal P-glycoprotein. Liposomal preparations of PSC833 may provide a useful alternative dosage form for intravenous administration of PSC 833 to be combined with anticancer drugs to circumvent drug resistance in cancer chemotherapy." @default.
• W1967778052 created "2016-06-24" @default.
• W1967778052 creator A5005730412 @default.
• W1967778052 creator A5010147133 @default.
• W1967778052 creator A5077847929 @default.
• W1967778052 date "2001-09-11" @default.
• W1967778052 modified "2023-09-27" @default.
• W1967778052 title "Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines" @default.
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• W1967778052 doi "https://doi.org/10.1016/s0168-3659(01)00406-0" @default.
• W1967778052 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11532308" @default.
• W1967778052 hasPublicationYear "2001" @default.
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