Engineering Polysaccharide-Based Polymeric Micelles to Enhance Permeability of Cyclosporin A Across Caco-2 Cells |
| |
Authors: | Mira F.?Francis,Mariana?Cristea,Yali?Yang,Franc?oise M.?Winnik author-information" > author-information__contact u-icon-before" > mailto:francoise.winnik@umontreal.ca" title=" francoise.winnik@umontreal.ca" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
| |
Affiliation: | (1) Faculty of Pharmacy, University of Montreal, Montreal, Quebec, H3C 3J7, Canada;(2) Petru Poni, Institute of Macromolecular Chemistry, Iasi, 700487, Romania;(3) Department of Chemistry, University of Montreal, Montreal, Quebec, H3C 3J7, Canada |
| |
Abstract: | No HeadingPurpose. 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. |
| |
Keywords: | Caco-2 cyclosporin A dextran hydroxypropylcellulose oral delivery P-glycoprotein polymeric micelles transport |
本文献已被 PubMed SpringerLink 等数据库收录! |
|