Intracellular pH-Sensitive PEG-<i>block</i>-Acetalated-Dextrans as Efficient Drug Delivery Platforms

Abstract

Intracellular pH-sensitive micelles of PEG-<i>block</i>-acetalated-dextran (PEG-<i>b</i>-AC-Dex) were prepared and used for acid-triggered intracellular release of anticancer drug. The hydrodynamic radii (<i>R</i>_h) of PEG-<i>b</i>-AC-Dex micelles could increase after incubation in PBS solution at pH 5.5. Based on the pH-responsive <i>R</i>_h variation behavior, it was expected that the PEG-<i>b</i>-AC-Dex micelles should be interesting for intracellular drug delivery. Thus, doxorubicin (DOX), a wide-spectrum anticancer drug, was loaded into the micelles and the pH-dependent release of the payload DOX was tested <i>in vitro</i>. The <i>in vitro</i> drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while up to about 90% of the loaded DOX could be quickly released in PBS solution at pH 5.5. Compared to pH-insensitive PEG-PLA micelles, the PEG-<i>b</i>-AC-Dex micelles displayed a faster drug release behavior in tumor cells. Moreover, higher cellular proliferation inhibition efficacy was achieved toward tumor cells. These features suggested that DOX could be efficiently loaded and delivered into tumor cells <i>in vitro</i> by the intracelluar pH-sensitive micelles, leading to enhanced inhibition of tumor cell proliferation. Therefore, the pH-sensitive micelles may provide a promising carrier for acid-triggered drug release for cancer therapy