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 IC 50 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.

Chitosan‐based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy

“…Furthermore, surface modification of micelles, for instance, with phenyboronic acid promotes selectivity toward tumor cells and enhances the tumor‐suppressor activity of DOX. 238 , 239 , 240 , 241 , 242 …”

“…The micelles can provide pH‐responsive release of DOX at the tumor site and provide co‐delivery of DOX with other antitumor agents such as cisplatin for synergistic cancer therapy. Furthermore, surface modification of micelles, for instance, with phenyboronic acid promotes selectivity toward tumor cells and enhances the tumor‐suppressor activity of DOX 238–242 …”

“…Furthermore, surface modification of micelles, for instance, with phenyboronic acid promotes selectivity toward tumor cells and enhances the tumor-suppressor activity of DOX. [238][239][240][241][242] The DOX-loaded micelles can be prepared using alginate and CS in a water-in-oil emulsion method with a spherical particle size of 80 nm. This is an interesting method for loading DOX in nanocarriers and uses an aqueous phase dispersed in a cyclohexane/dodecylamine organic phase.…”

Chitosan Functionalization: Covalent and Non-Covalent Interactions and Their Characterization

“…Most reports present the use of EDC.HCl in combination with N-hydroxysuccinimide (NHS) or hydroxybenzotriazole (HOBt) to improve the stability of the activated intermediates prior to conjugation with CS amines [ 28 , 29 , 30 , 31 , 32 ]. Some substrates of interest are also supplied as NHS ester derivatives, thus facilitating their coupling with CS.…”