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±15nm and -39.5±0.33mV, respectively. The concentration of PTX loaded in the NEs was 6mg/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°C for 12 months and the reconstituted HNE solution was stable for at least 96h, even though Taxol^® can be maintained for only 72h. 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.