Phenylboronic acid-functionalized F127-oligochitosan conjugate micelles for doxorubicin encapsulation.

ABSTRACT

Doxorubicin shows good anticancer activity, but poor pharmacokinetic property and high organ toxicity restrict its clinical application. The synthesized phenylboronic acid-modified F127-chitosan conjugate was used to prepare doxorubicin-loaded micelles through dialysis method. The physicochemical properties of the doxorubicin-loaded micelles were characterized. These micelles were further evaluated for in vitro release/cytotoxicity, in vivo activity/biosafety, and pharmacokinetic studies. in vitro release experiment demonstrated that the release of doxorubicin from drug-loaded micelles was pH-dependent. in vitro cytotoxic study showed that the introduction of phenylboronic acid resulted in lower IC50 against B16 cells than that in non-modified F127-chitosan micelles group, and the doxorubicin-loaded micelles displayed lower in vitro activity against B16, A549, and HT-29 cells than free doxorubicin did. However, in vivo experiments confirmed that the doxorubicin-loaded micelles were safe for mouse main organs, obviously improved pharmacokinetic parameters of doxorubicin in rat and achieved comparable inhibition of tumor growth with no animal death in B16-bearing mice models throughout the experiment when compared with free doxorubicin. The phenylboronic acid-sialic acid interaction and pH-sensitive drug release might play important roles in increased tumor targeting and therapeutic effect of the doxorubicin-loaded micelles.