Encapsulation and pH-responsive release of bortezomib by dopamine grafted hyaluronate nanogels.

ABSTRACT

Hydrophobic drugs loaded nanogels were always associated with low encapsulation efficiency and immature burst release. In this work, dopamine grafted hyaluronate nanogels were designed for bortezomib (BTZ), a hydrophobic anticancer drug and a proteasome inhibitor. It was found that there was a more efficient loading and pH-controlled release of BTZ due to the presence of dopamine groups on the skeleton of the nanogels. The drug loading content (DLC) were up to 8.58% as the nanogels modified with 29% dopamine, compared to the DLC of less than 1% for nanogels without dopamine modification. It was the pH-sensitive nature of the borated bonds between BTZ and catechol groups that endowed the pH-responsive release behavior of BTZ in vitro. In vitro study proved good biocompatibility and efficient cell uptake of the nanogels. In vivo anti-tumor experiments demonstrated that bortezomib loading into the nanogel significantly enhanced the therapeutic effect of the drug. After 14-day treatment, the average tumor volume of BTZ loaded nanogel group was reduced by 200% more than that of free BTZ group. Combined with CD44 receptor targeting ability of hyaluronate and the merits of nanogel, the catechol modified hyaluronate nanogel exhibited as an efficient chemotherapeutic formulation of BTZ for cancer treatment.