Solubilization of an amphiphilic drug by poly(ethylene oxide)- block-poly(ester) micelles

Abstract

The purpose of this study was to investigate the solubilization of an amphiphilic drug, i.e, amiodarone (AMI) in methoxy poly(ethylene oxide)- block-poly(ester) micelles of different core structure. The effect of core-forming block structure as well as molecular weight, applied drug to polymer ratios and assembly condition on AMI solubilization; stability of the solubilized formulation upon dilution in phosphate buffer and the hemolytic activity of solubilized AMI against rat red blood cells were assessed and compared to those parameters for the commercial intravenous formulation of AMI. In general, polymeric micelles of different core structure were found to be more efficient in retaining their AMI content upon dilution than surfactant micelles in the commercial formulation of AMI for injection. Micelles with a poly( ε-caprolactone) (PCL) core were more efficient than poly( d, l-lactide) and poly( l-lactide) cores in the solubilization and stabilization of encapsulated AMI within the carrier. Encapsulation of AMI by methoxy poly(ethylene oxide)- block- poly( ε-caprolactone) (MePEO- b-PCL) micelles having higher PCL chains increased the level of AMI solubilization and decreased its hemolytic activity. Compared to O/W emulsion, application of solvent evaporation method led to higher encapsulation efficiency and lower hemolytic activity for AMI in micelles. An increase in the level of AMI added to the co-solvent evaporation process led to an increase in the solubilized AMI levels, but made the formulation more hemolytic. In conclusion, PEO- b-PCL micelles, particularly those with longer PCL chains, were found to be efficient carriers in encapsulating amphiphilic AMI, retaining encapsulated AMI within the carrier and reducing its hemolytic activity.