Interactions between a triblock copolymer and hydroxyethyl cellulose in aqueous solution and their use in the solubilization of Amiodarone

Abstract

A physicochemical characterization of the mixtures of triblock copolymer PEO20-PPO70-PEO20, (P123) and hydroxyethyl cellulose (HEC) in aqueous solutions, with and without the hydrophobic drug amiodarone (ADA), was performed by pendant drop tensiometry, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). The results allowed us to propose a detailed diagram for the formation of the different aggregates in water. The equilibrium surface tension values showed that adding HEC to P123 solutions promotes the aggregation of the P123 monomers on the HEC polymer until saturation. By adding ADA into the P123 micelles, the same equilibrium surface tension values were obtained as the ones found in the pure solution of P123. This suggests that the drug is mostly encapsulated. The DSC experiments showed that the critical micelle temperature and the enthalpy of aggregation of P123 were not modified by the presence of HEC. But the incorporation of ADA to the micelles showed a reduction of 40% in the enthalpy of aggregation, indicating a strong interaction between P123 and ADA. In contrast to the empty micelles, when HEC is added to the loaded micelles, the enthalpy of aggregation increases and the interaction of HEC-P123 becomes evident. The DLS results support that the hydrodynamic diameter of the ADA-loaded micelles is 17% smaller than the diameter of the empty P123 micelles. In the presence of HEC, the empty or loaded micelles form a larger complex. This suggests that HEC surrounds the micelles and provides the drug with a second protecting shell. This system could be a good candidate for the hydrophobic drug delivery.