Document Detail


Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid.
MedLine Citation:
PMID:  11299776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Y L Lo; F I Liu; J M Yang; J Y Cherng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 Jan-Feb
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-05-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  445-50     Citation Subset:  IM    
Affiliation:
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.net
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*,  metabolism
Animals
Antibiotics, Antineoplastic / pharmacokinetics*,  pharmacology
Biological Transport
Caco-2 Cells
Cell Membrane Permeability
Colonic Neoplasms / drug therapy*,  metabolism
Cyclosporine / administration & dosage*,  pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Multiple*
Drug Resistance, Neoplasm
Epirubicin / pharmacokinetics*,  pharmacology
Fat Emulsions, Intravenous / metabolism
Humans
Intestines / metabolism
Kinetics
Liposomes / metabolism
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Fat Emulsions, Intravenous; 0/Liposomes; 56420-45-2/Epirubicin; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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