Engineering polysaccharide-based polymeric micelles to enhance permeability of cyclosporin A across Caco-2 cells.

purposeTo 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.

methodsDextran (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.

resultsThe 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.

conclusionsPolysaccharide-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.