Preparation of hyaluronic acid-decorated mixed nanomicelles for targeted delivery of hydrophobic drugs to CD44-overexpressing cancer cells

Most of the employed methods for preparation of targeted nanoparticles containing hydrophobic herbal drugs have multiple surface modifications with time-consuming steps. The present research was aimed to develop a facile method for preparation of hyaluronic acid (HA)-decorated mixed nanomicelles loaded with curcumin (as a hydrophobic drug model) to provide an efficient drug delivery system for targeted therapy of breast cancer cells with high expression of CD44 receptor. To this end, curcumin was first encapsulated in the hydrophobic core of Pluronic F127/didecyldimethylammonium bromide (PD) mixed nanomicelles using thin-film hydration method. Then, negatively charged HA was coated on the positively charged surface of PD mixed nanomicelles via electrostatic interactions. The drug loading and entrapment efficiency of the targeted nanomicelles were 2.8% and 95.1%, respectively. The average hydrodynamic size of the prepared nanomicelles before and after coating with HA were 19.8 and 35.8 nm, respectively. Moreover, in vitro cytotoxicity analyses showed that, HA-coated PD (HA-PD) mixed nanomicelles can enhance the cytotoxicity of curcumin against MDA-MB-231 cancer cells compared to non-targeted ones (PD mixed nanomicelles), and free curcumin. The IC₅₀ concentrations of free curcumin, curcumin-loaded PD mixed nanomicelles, and curcumin-loaded HA-PD mixed nanomicelles were 4.11, 3.20, and 2.83 μg/mL, respectively, after 48 h incubation with MDA-MB-231 cancer cells. Our results suggest that, curcumin-loaded HA-PD mixed nanomicelles may be considered as a promising targeted anticancer drug delivery system for breast cancer therapy and/or delivering other hydrophobic drugs to different kinds of cancer cells with CD44-receptor overexpression.