High paclitaxel-loaded and tumor cell-targeting hyaluronan-coated nanoemulsions

The purpose of this study was to develop hyaluronan-coated nanoemulsions (HNEs) with high solubilizing capacity and tumor cell targeting capability for the poorly soluble paclitaxel. The HNEs were composed of DL-a-tocopheryl acetate, soybean oil, polysorbate 80, and ferric chloride and were coated with hyaluronic acid (HA) as a targeting moiety. The nanoemulsions (NEs) and HNEs with or without paclitaxel (PTX) were prepared using high-pressure homogenization with a microfluidizer and were lyophilized with D-mannitol. The particle diameter and zeta potential of the HNEs were 65 +/- 15 nm and -39.5 +/- 0.33 mV, respectively. The concentration of PTX loaded in the NEs was 6 mg/mL, which was higher than that in any other nanocarrier. The HNEs were coated with HA on the outer surface of the sphere and the amount of HA was 0.82 +/- 0.10% (w/w). The lyophilized formulation was stable at 4 degrees C for 12 months and the reconstituted HNE solution was stable for at least 96 h, even though Taxol (R) can be maintained for only 72 h. In the cell affinity studies with SK-OV-3 (cluster of differentiation 44 [CD44](+)) and OVCAR-3 (CD44(-)) cells, the HNEs displayed a 10-fold higher targeting capability than the NEs did. Therefore, the HNEs displayed high drug loading capability, excellent stability, and targeting of tumor cells overexpressing CD44, which suggested they were a potentially effective nanocarrier for carrying poorly soluble paclitaxel and targeting tumors. (C) 2016 Elsevier B.V. All rights reserved.