A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel

摘要

In order to achieve enhanced and synergistic delivery of paclitaxel (PTX), a hydrophobic anticancer agent, two novel prodrug copolymers, POEG(15)-b-PFTS6 and POEG(15)-b-PFTS16 composed of hydrophilic poly (oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks, were synthesized. Both POEG-b-PFTS polymers were able to form micelles with intrinsic antitumor activity in vitro and in vivo. Employing these micelles as a carrier to load PTX, their drug loading capacity, stability, in vivo biodistribution and tumor inhibition effect were evaluated. PTX/POEG(15)-b-PFTS16 mixed micelles exhibited an excellent stability of 9 days at 4 degrees C with a PTX loading capacity of 8.2%, which was more effective than PTX/POEG(15)-b-PFTS6 mixed micelles. In vivo biodistribution data showed that DiR-loaded POEG-b-PFTS micelles were more effectively localized in the tumor than in other organs. Moreover, both PTX/POEG-b-PFTS micelles showed significantly higher antitumor activity than Taxol in a 4T1.2 murine breast tumor model, and the tumor inhibition and animal survival followed the order of PTX/POEG(15)-b-PFTS16 > PTX/POEG(15)-b-PFTS6 > POEG(15)-b-PFTS16 > Taxol approximate to OEG(15)b-PFTS6. Our data suggest that POEG-b-PFTS micelles are a promising anticancer drug carrier that warrants more studies in the future.