Synthesis and optimization of a novel polymeric micelle based on hyaluronic acid and phospholipids for delivery of paclitaxel, in vitro and in-vivo evaluation

Novel polymeric micelles were synthesized based on hyaluronic acid (HA) and phospholipids (PEs) including 1,2-dimiristoyl phosphatidylethanolamine (DMPE) and 1,2-distearoyl phosphatidylethanolamine (DSPE). The newly developed micelles evaluated for the physicochemical properties including structural analysis by means of FTIR. Micelles were optimized for delivery of paclitaxel (PTX). The D-optimal design was applied in order to reach micelles with high entrapment efficiency (EE %) and minimum size, simultaneously. In this design the independent variables were the co-polymer type, the drug to polymer ratio and the formulation temperature, whereas the dependent variables were EE% and micelle size. The EE% of the optimized micelles was 46.8% and 59.9% for HA-DMPE and HA-DSPE micelles, respectively. The size of the optimized micelles was in the range of around 250 nm. In vitro release study of the optimized micelles showed that PTX was released from HA-DMPE and HA-DSPE micelles as long as 23 h and 34 h, respectively. Differential scanning calorimetry (DSC) studies showed a conversion of the crystalline PTX molecules into the amorphous form in the micelles. In vivo real time image analysis showed that micellar system was mostly accumulated in the liver, spleen and heart. Accelerated stability studies represented that PTX loaded micelle formulations were stable both physically and chemically at least in 6 months' time. (C) 2014 Elsevier B.V. All rights reserved.