Polyelectrolyte Multilayer Nanoshells With Hydrophobic Nanodomains for Delivery of Paclitaxel

Delivery of poorly water-soluble drug molecules, which constitute a large part of commercially available drugs, is a major challenge. Several drugs including paclitaxel (PTX) that are used for cancer treatment are hydrophobic and need to be delivered using an appropriate carrier. Here we engineered PTX-loaded polyelectrolyte films and microcapsules by pre-complexing PTX with alkylamino hydrazide derivatives of HA, and subsequent assembly with either poly(L-lysine) (PLL) or quaternized chitosan (QCHI) as polycations. The PTX loading capacity of the films was found to be dependent on the number of layers in the films as well as on the initial concentration of PTX pre-complexed to hydrophobic HA, with a loading capacity up to 5000-fold the initial PTX concentration. The films were stable in physiological medium and were degraded in the presence of hyaluronidase. The PTX-loaded microcapsules were found to decrease the viability and proliferation of MDA-MB-231 breast cancer cells, while unloaded microcapsules did not impact cell viability. All together, our results highlight the potential of hyaluronan-based assemblies for hydrophobic drug delivery.