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Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines.
J Control Release. 2001 Sep 11; 76(1-2):1-10.JC

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.

Authors+Show Affiliations

Department of Pharmacy, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Section 1, Jen-Te, 717, Tainan, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11532308

Citation

Lo, Y, et al. "Effect of PSC 833 Liposomes and Intralipid On the Transport of Epirubicin in Caco-2 Cells and Rat Intestines." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 76, no. 1-2, 2001, pp. 1-10.
Lo Y, Liu F, Cherng J. Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines. J Control Release. 2001;76(1-2):1-10.
Lo, Y., Liu, F., & Cherng, J. (2001). Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines. Journal of Controlled Release : Official Journal of the Controlled Release Society, 76(1-2), 1-10.
Lo Y, Liu F, Cherng J. Effect of PSC 833 Liposomes and Intralipid On the Transport of Epirubicin in Caco-2 Cells and Rat Intestines. J Control Release. 2001 Sep 11;76(1-2):1-10. PubMed PMID: 11532308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines. AU - Lo,Y, AU - Liu,F, AU - Cherng,J, PY - 2001/9/5/pubmed PY - 2001/10/12/medline PY - 2001/9/5/entrez SP - 1 EP - 10 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 76 IS - 1-2 N2 - 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. SN - 0168-3659 UR - https://www.unboundmedicine.com/medline/citation/11532308/Effect_of_PSC_833_liposomes_and_Intralipid_on_the_transport_of_epirubicin_in_Caco_2_cells_and_rat_intestines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168365901004060 DB - PRIME DP - Unbound Medicine ER -