Mineralized hyaluronic acid nanoparticles as a robust drug carrier

摘要

Hyaluronic acid nanoparticles (HA-NPs), mineralized by calcium phosphate, were synthesized as a robust carrier of the anticancer drug, doxorubicin (DOX). The HA-NPs were readily mineralized in the presence of calcium nitrate and ammonium phosphate, which was confirmed by various instruments such as FT-IR, thermogravimetric analysis, transmission electron microscopy, and energydispersive X-ray photoelectron spectroscopy. Mineralization reduced the particle size of the HA-NPs in PBS (pH 7.4) from 263 nm to 142 ntn, indicating the formation of compact nanoparticles. Mineralized HA-NPs were highly stable at pH 7.4, whereas their particle size rapidly increased in a mildly acidic solution, which was due to the dissolution of calcium phosphate. When DOX-loaded bare HA-NPs were exposed to buffer solutions of various pH, most of the DOX (>80%) was released within 48 h, and the release behavior was not dependent upon the pH of the solution. Notably, the mineralized HA-NPs released DOX in a sustained manner at pH 7.4, whereas a rapid release of DOX was observed in the acidic solution. The release rate of DOX from the mineralized HA-NPs was higher in the solution with a lower pH. These results indicate that mineralized HA-NPs have potential as robust nanoparticles that can release DOX at specific sites under mildly acidic conditions, such as in the extracellular matrix of tumor tissue and in intracellular compartments {e.g., endosome and lysosome) of the cell.