Document Detail

Polymeric micelles for the solubilization and delivery of cyclosporine A: pharmacokinetics and biodistribution.
MedLine Citation:
PMID:  16005061     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to assess the potential of polymeric micelles to modify the pharmacokinetics and tissue distribution of cyclosporine A (CsA). Drug-loaded methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) micellar solutions in isotonic medium were prepared and administered intravenously to healthy Sprague-Dawley rats. Blood and tissues were harvested and assayed for CsA, and resultant pharmacokinetic parameters and tissue distribution of CsA in its polymeric micellar formulation were compared to its commercially available intravenous formulation (Sandimmune). In the pharmacokinetic assessment, a 6.1 fold increase in the area under the blood concentration versus time curve (AUC) was observed for CsA when given as polymeric micellar formulation as compared to Sandimmune. The volume of distribution and clearance of CsA as PEO-b-PCL formulation were observed to be 10.0 and 7.6 fold lower, respectively, compared to the commercial formulation. No significant differences in t(1/2) or MRT could be detected. In the biodistribution study, analysis of tissue samples indicated that the mean AUC of CsA in polymeric micelles was lower in liver, spleen and kidney (1.5, 2.1 and 1.4-fold, respectively). Similar to the pharmacokinetic study in these rats, the polymeric micellar formulation gave rise to 5.7 and 4.9-fold increase in the AUC of CsA in blood and plasma, respectively. Our results show that PEO-b-PCL micelles can effectively solubilize CsA, at the same time confining CsA to the blood circulation and restricting its access to tissues such as kidney, perhaps limiting the onset of toxicity.
Hamidreza Montazeri Aliabadi; Dion R Brocks; Afsaneh Lavasanifar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biomaterials     Volume:  26     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-08-16     Completed Date:  2005-10-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  7251-9     Citation Subset:  IM    
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada T6G 2N8.
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MeSH Terms
Coated Materials, Biocompatible / chemistry
Cyclosporine / administration & dosage*,  chemistry,  pharmacokinetics*
Drug Carriers / chemistry*
Immunosuppressive Agents / administration & dosage
Injections, Intravenous
Materials Testing
Metabolic Clearance Rate
Organ Specificity
Polyesters / analysis,  chemistry*
Polymers / chemistry
Rats, Sprague-Dawley
Tissue Distribution
Vehicles / chemistry*
Reg. No./Substance:
0/Coated Materials, Biocompatible; 0/Drug Carriers; 0/Immunosuppressive Agents; 0/Micelles; 0/Polyesters; 0/Polymers; 0/Vehicles; 0/polyethylene oxide-polycaprolactone copolymer; 59865-13-3/Cyclosporine

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

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