Dual Redox/pH-Sensitive Micelles Self-Assembled From Star-Like Amphiphilic Copolymers Based On Sucrose For Controlled Doxorubicin Delivery

Novel dual redox/pH-sensitive star-like amphiphilic sucrose-oligo(butyl fumarate) (thioglycolic acid conjugate)-SS-poly(ethylene glycol) (Suc-OBF(TGA)-SS-PEG) copolymers and their self-assembled micelles were prepared and utilized for intracellular doxorubicin delivery. Importance of changing the hydrophobic chain length on micelles properties was investigated. Results showed that the micelles with longer hydrophobic chain exhibited smaller size and were more stable in aqueous solution. The redox and pH sensitivity of the micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic light scattering and the change of micellar morphology observed by scanning electron microscope. The micelles display a decent doxorubicin loading capacity. In vitro release studies showed that only 14.3% doxorubicin was released from doxorubicin-loaded micelles under physiological conditions in 30 h. The release of doxorubicin was accelerated at pH 5.5 or in the presence of 10 mM glutathione at pH 7.4 (46.9% and 76.9% of doxorubicin was released, respectively, in 30 h). The doxorubicin release was further expedited under pH 5.5 and 10 mM GSH conditions (91.4%). Suc-OBF(TGA)-SS-PEG micelles displayed no cytotoxicity toward HDF cells. MTT assays indicated that doxorubicin-loaded micelles had good cytotoxicity against MCF-7 cells. This work suggested that star-like amphiphilic SucOBF(TGA)-SS-PEG copolymer micelles may provide a promising platform for delivering doxorubicin and other hydrophobic anticancer drugs. (C) 2021 Published by Elsevier Inc. on behalf of the American Pharmacists Association.