Pharmaceutical Research

, Volume 22, Issue 2, pp 209–219

Engineering Polysaccharide-Based Polymeric Micelles to Enhance Permeability of Cyclosporin A Across Caco-2 Cells

  • Mira F. Francis
  • Mariana Cristea
  • Yali Yang
  • Francçoise M. Winnik
Research Papers

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Purpose.

To assess and compare the effectiveness of two types of polysaccharide-based micelles as delivery vehicles for poorly water soluble drugs by monitoring their permeability across Caco-2 cell monolayers.

Methods.

Dextran (DEX) and hydroxypropylcellulose (HPC) were hydrophobically modified (HM) by grafting polyoxyethylene cetyl ether (POE-C16, 15 mol% and 5.4 mol%, respectively). The onset of micellization and mean diameter of polymeric micelles formed by HM-DEX and HM-HPC were determined by fluorescence spectroscopy and dynamic light scattering, respectively. Cyclosporin A (CsA)-loaded polymeric micelles were prepared by a dialysis procedure, and the amount of incorporated CsA was assayed by high performance liquid chromatography (HPLC). The stability of micelles in simulated gastric and intestinal fluids was studied as a function of contact time, and their cytotoxicity toward Caco-2 cells was evaluated using the MTT colorimetric assay. The bidirectional transport across Caco-2 cell monolayers of CsA entrapped in HM-DEX and HM-HPC micelles and of the polymers themselves was evaluated in the presence and absence of P-glycoprotein inhibitor.

Results.

The amount of CsA incorporated in HM-HPC and HM-DEX micelles reached 5.5 and 8.5% w/w, respectively (entrapment efficiency of 22% or more). The polymeric micelles exhibited high stability in gastric and intestinal fluids and no significant cytotoxicity toward Caco-2 cells. The apical to basal permeability of CsA across Caco-2 cells increased significantly when loaded in polymeric micelles compared to free CsA.

Conclusions.

Polysaccharide-based polymeric micelles are promising carriers for the oral delivery of poorly water soluble drugs. In vitro tests indicate that, overall, HM-HPC micelles are more effective compared to HM-DEX micelles.

Key Words:

Caco-2 cyclosporin A dextran hydroxypropylcellulose oral delivery P-glycoprotein polymeric micelles transport 

Abbreviations

AP

apical side

BL

basolateral side

CsA

cyclosporin A

DEX

dextran T10

HPC

hydroxypropylcellulose

P85

Pluronic P85

PGI

P-glycoprotein inhibitor

P-gp

P-glycoprotein

POE-C16

polyoxyethylene (10) cetyl ether

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Mira F. Francis
    • 1
  • Mariana Cristea
    • 2
  • Yali Yang
    • 3
  • Francçoise M. Winnik
    • 1
    • 3
  1. 1.Faculty of PharmacyUniversity of MontrealMontreal, QuebecCanada
  2. 2.“Petru Poni”Institute of Macromolecular ChemistryIasiRomania
  3. 3.Department of ChemistryUniversity of MontrealMontreal, QuebecCanada

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