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Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid.
Anticancer Res. 2001 Jan-Feb; 21(1A):445-50.AR

Abstract

Clinical applications of the first-generation multidrug resistance (MDR) modulators, such as cyclosporin A (CsA) have been hampered because of their severe side effects in vivo. In this study, we utilized liposomes and Intralipid to provide selective delivery of CsA to tumor cells as well as to circumvent toxicities associated with CsA by altering the pharmacodistribution properties of encapsulated CsA. The MDR reversing effect of CsA in free, liposomal or Intralipid formulations on the uptake and transport of epirubicin in Caco-2 cells and rat intestines was evaluated. The results showed that CsA in free or liposomal formulations significantly enhanced the intracellular accumulation of epirubicin in a dose-related fashion in Caco-2 cells, with the highest enhancement at 2 microM: These formulations substantially ameliorated the apical to basolateral absorption of epirubicin in Caco-2 cells and markedly increased mucosal to serosal absorption of epirubicin in rat jejunum and ileum. CsA in free, liposomal or Intralipid formulations all significantly reduced basolateral to apical efflux of epirubicin across Caco-2 monolayers. CsA encapsulated in liposomes showed greater enhancement than other formulations. In conclusion, liposomal preparations of CsA may circumvent MDR and have the advantage of diminishing side effects, thus providing a useful alternative dosage form for intravenous administration of CsA to be combined with cytotoxic agents for the treatment of resistant tumors.

Authors+Show Affiliations

Department of Pharmacy, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Sec. 1, Jen-Te Hsiang, Tainan Hsien 717, Taiwan, R.O.C. yulilo@ms17.hinet.netNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11299776

Citation

Lo, Y L., et al. "Reversal of Multidrug Resistance to Epirubicin By Cyclosporin a in Liposomes or Intralipid." Anticancer Research, vol. 21, no. 1A, 2001, pp. 445-50.
Lo YL, Liu FI, Yang JM, et al. Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid. Anticancer Res. 2001;21(1A):445-50.
Lo, Y. L., Liu, F. I., Yang, J. M., & Cherng, J. Y. (2001). Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid. Anticancer Research, 21(1A), 445-50.
Lo YL, et al. Reversal of Multidrug Resistance to Epirubicin By Cyclosporin a in Liposomes or Intralipid. Anticancer Res. 2001 Jan-Feb;21(1A):445-50. PubMed PMID: 11299776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid. AU - Lo,Y L, AU - Liu,F I, AU - Yang,J M, AU - Cherng,J Y, PY - 2001/4/13/pubmed PY - 2001/5/5/medline PY - 2001/4/13/entrez SP - 445 EP - 50 JF - Anticancer research JO - Anticancer Res VL - 21 IS - 1A N2 - Clinical applications of the first-generation multidrug resistance (MDR) modulators, such as cyclosporin A (CsA) have been hampered because of their severe side effects in vivo. In this study, we utilized liposomes and Intralipid to provide selective delivery of CsA to tumor cells as well as to circumvent toxicities associated with CsA by altering the pharmacodistribution properties of encapsulated CsA. The MDR reversing effect of CsA in free, liposomal or Intralipid formulations on the uptake and transport of epirubicin in Caco-2 cells and rat intestines was evaluated. The results showed that CsA in free or liposomal formulations significantly enhanced the intracellular accumulation of epirubicin in a dose-related fashion in Caco-2 cells, with the highest enhancement at 2 microM: These formulations substantially ameliorated the apical to basolateral absorption of epirubicin in Caco-2 cells and markedly increased mucosal to serosal absorption of epirubicin in rat jejunum and ileum. CsA in free, liposomal or Intralipid formulations all significantly reduced basolateral to apical efflux of epirubicin across Caco-2 monolayers. CsA encapsulated in liposomes showed greater enhancement than other formulations. In conclusion, liposomal preparations of CsA may circumvent MDR and have the advantage of diminishing side effects, thus providing a useful alternative dosage form for intravenous administration of CsA to be combined with cytotoxic agents for the treatment of resistant tumors. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/11299776/Reversal_of_multidrug_resistance_to_epirubicin_by_cyclosporin_A_in_liposomes_or_intralipid_ DB - PRIME DP - Unbound Medicine ER -