Journal
LANGMUIR
Volume 39, Issue 33, Pages 11839-11850Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.3c01576
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An injectable hydrogel based on self-assembled micelles of a Vitamin E derivative α-TOS was developed for combined chemotherapy. The hydrogel sustained released the loaded drug over 7 days and demonstrated synergistic antitumor effects with minimal toxic side effects.
Vitamin E derivatives are particularly effective in chemotherapydrug development because they are nontoxic, biocompatible, and selective.Among them, & alpha;-tocopheryl succinate (& alpha;-TOS) can act synergisticallywith some chemotherapeutic agents. However, its hydrophobicity limitsits systemic administration, and localized formulations are not available.Herein, we developed an injectable hydrogel based on self-assembledmicelles of a triblock amphiphilic derivative of & alpha;-TOS (PEG-2VES),in which doxorubicin (DOX) was encapsulated in the core of the micellesfor combined chemotherapy. A molecule of & alpha;-TOS was grafted ontoeach end of poly(ethylene glycols) (PEGs) of different lengths. Hydrogelswere prepared by dissolving the polymers or the DOX-loaded micellesin water at room temperature. The subcutaneously injected hydrogelskept their shape and sustainably released the payloads over 7 dayswithout any noticeable inflammatory response. In vitro and in vivoresults confirmed the synergistic antitumor effects of the hydrogeland loaded drug. Furthermore, DOX-loaded hydrogels showed greatertherapeutic efficiency and fewer toxic side effects than DOX alone.Overall, this hydrogel acts as a multifunctional system that can deliverdrug, improve the therapeutic effect, and minimize drug toxicity.
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