Paclitaxel solubilized nanoparticles based on binding affinity for efficient drug delivery

Paclitaxel (PTX), a typical chemotherapeutic agent, was restricted in clinical cancer treatment as its poor water solubility (-0.25 & mu;g/mL). This study firstly prepared the thioether-bridged polymer-drug conjugates HAACP and HPP based on hyaluronic acid (HA) to address the poor water solubility of PTX. After the structure confirmed by 1H NMR and MS, the biocompatibility of the conjugates was evaluated. The hydrolyzed profiles of thioether-bridged conjugates were also determined in H2O2 to release free PTX, indicating the particular release kinetic at the tumor microenvironment. The binding capacity between the conjugates and PTX was investigated by critical aggregation concentration (cac) as an attractive interaction, which further proved to be a strong syn-ergism when the mole fraction of PTX was less than or equal to 0.2. Nanoparticles HPP-PTX4 were demonstrated a largest solubility enhancement ratio (4338.49) of PTX than other nanoparticles, which indicated the effective solubilization (-1 mg/mL). Wound healing assays and cytotoxicity had been conducted to prove the inhibition of the nanoparticles for the cancer cells and non-toxic property for normal cells. Cellular uptake studies not only reflected the effective internalization of the nanoparticles, but also proved the HA-mediated active targeting behavior. The cell arrest mechanism for mitosis was evaluated by apoptosis and cell cycle assays and further apoptosis. 3D spheres models were established to mimic the tumor in vivo to investigate the inhibition and penetration capacity of the nanoparticles for cancer cells. In view of the experiments, we thought the synthesized conjugate could represent as the promising drug delivery for the hydrophobic drugs, and thus hold tremendous potentials for anti-tumor treatment.

Automated summary

This study prepared thioether-bridged polymer-drug conjugates based on hyaluronic acid to address the poor water solubility of paclitaxel. The conjugates showed good biocompatibility and a particular release kinetic at the tumor microenvironment. The nanoparticles exhibited enhanced solubility of paclitaxel and demonstrated effective inhibition of cancer cells with no toxicity to normal cells.