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

In this paper, pi-pi 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 pi-pi 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 pi-pi conjugated small molecules as lipophilic moieties could be serve as a universal prototype for drug delivery.