Amphiphilic conjugates for solubilization of paclitaxel as efficient drug carriers based on hyaluronic acid and cyclodextrins

Abstract

Despite paclitaxel (PTX) as the first-line anti-tumor drugs, the unsatisfactory low-solubility in water remained a barrier to clinical application. Thus, the present study aimed at enhancing the solubility of PTX. Accordingly, we designed the amphiphilic conjugates (HP) as the delivery system and prepared self-assembly nanoparticles by the conjugates. Hemolysis assays showed the good biocompatibility of the conjugates. Meanwhile, binding affinity between the conjugates and PTX was explored based on the critical aggregation concentration (cac). The biggest solubilization for the nanoparticles was 193.56-fold, which exhibited as the solubility of 48.39 μg/mL. Cellular uptake assays revealed the valid internalization of nanoparticles and the targetability. In addition, the nanoparticles arrested the mitosis and further apoptosis. Cytotoxicity and three-dimensional multicellular spheroid (3DMCS) assays proved the strong growth inhibition capacity and the superior penetration ability for the nanoparticles. These results suggested that the HP conjugate we synthesized could provide potential insights into the delivery system for hydrophobic drugs on the aspects of anti-tumor.