Hyaluronic acid hydrophilic surficial rehabilitative curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution
Natural bioactive curcumin has attracted more and more attention as a potential antineoplastic drug for their high therapeutic efficiency and low systemic toxicity. Though the emergence of carrier-free nanocrystalline technology could improve the solubility and guarantee high drug loading of curcumin, the uncontrollable drug release, and fast systemic metabolism are definitely obstacles for their further application in cancer treatment. Here, hyaluronic acid (HA) modification was formulated on the surface of curcumin nanocrystals (Cur-NC) to obtain surficial hydrophilicity reformed HA@Cur-NC as a function of prolonged biodistribution. Besides, HA@Cur-NC showed an enhanced intracellular uptake in CD44 overexpressing MDA-MB-231 cells but reduced when pre-treated with HA. The apoptotic effects confirmed by flow cytometry suggested that HA@Cur-NC could achieve high anticancer activity against the MDA-MB-231 cells. In vivo pharmacokinetic studies gave that the t1/2 and MRT of Cur were significantly extended after intravenous administration of HA@Cur-NC in normal rats. Moreover, HA@Cur-NC demonstrated a superior anticancer effect in a murine 4T1 orthotopic breast cancer model compared with free drug and Cur-NC. Overall, these results show the potential of HA@Cur-NC as a suitable formula for breast cancer therapy.