Combination of a chemopreventive agent and paclitaxel in CD44-targeted hybrid nanoparticles for breast cancer treatment.

The CD44 receptor, which is upregulated in many cancer cells, provides a selective cellular surface for targeted drug delivery systems. We developed a hybrid nanocarrier for the CD44-targeted delivery of ibuprofen (IBU) and paclitaxel (PTX). The solid lipid nanoparticles (SLNs) were prepared by a hot-melt oil/water emulsion technique and then coated with hyaluronic acid (HA) by electrostatic interactions. The final SLN were spherical with a hydrodynamic diameter (Z) of 72.16 ± 2.9 nm, polydispersity index (PDI) of 0.276 ± 0.009, and zeta potential (ZP) of 28.20 ± 0.69 mV. Similarly, SLN coated with HA (SLN-HA) exhibited acceptable physical properties (Z 169.3 ± 0.55 nm, PDI 0.285 ± 0.004, and ZP - 10.5 ± 0.15 mV). Cell viability assays showed that the combination of IBU, a chemopreventive agent, and PTX exerted a synergistic inhibitory effect on the proliferation of cancer cells (CI < 1.0). Additionally, our observations indicated that both SLN and SLN-HA enhanced apoptosis and cellular uptake compared to the cocktail of free drugs. HA indicated its affinity for cancer cells through the improvement of cellular uptake and induction of apoptosis. These results clearly indicated that these nanoparticle systems hold great promise for drug delivery in breast cancer treatment.