Polymeric micelles with π–π conjugated cinnamic acid as lipophilic moieties for doxorubicin delivery

Abstract

In this paper, π–π conjugated cinnamic acid (CIN) was used as a lipophilic moiety to fabricate polymeric micelles. The amphiphiles with one or two cinnamic acid molecules as lipophilic architectures (mPEG–CIN and mPEG–Lys–DCIN) were synthesized. We expressly investigated the effect of the lipophilic parts on size, morphology and stability of the self-assembly micelles. Anticancer drug doxorubicin (DOX) was trapped in the micelles and the interactions between the lipophilic moieties and DOX were studied. The anticancer activity of the DOX-loaded micelles was evaluated both in vitro and in vivo. The results revealed that mPEG–Lys–DCIN micelles exhibited better stability and higher drug loading content. Strong π–π stacking interaction was formed within the DOX-loaded micelles. The DOX released from mPEG–Lys–DCIN micelles was slower than that from mPEG–CIN micelles. DOX-loaded mPEG–Lys–DCIN micelles exhibit higher inhibition efficiency both in vitro and in vivo. Furthermore, the in vivo experimental results demonstrated that the anticancer efficiency of DOX-loaded mPEG–Lys–DCIN micelles was comparable to that of free DOX, meanwhile, the side effect of DOX was reduced greatly after encapsulation. This novel strategy of fabricating polymeric micelles with π–π conjugated small molecules as lipophilic moieties could be serve as a universal prototype for drug delivery.