Exquisite Vesicular Nanomedicine by Paclitaxel Mediated Co-assembly with Camptothecin Prodrug

We report that the self-assembly of drug amphiphiles, Evans blue conjugated camptothecin prodrug (EB-CPT), can be modulated by another anticancer drug paclitaxel (PTX), resulting in ultrahigh quality of nanovesicles (NVs) with uniform shape and diameters of around 80 nm with the EB-CPT:PTX weight ratio of 1:1, 1:2, and 1:3, denoted as ECX NVs. Significantly, the co-assembly of EB-CPT and PTX without adding other excipients has nearly 100 % drug loading efficiency (DLE) and ultrahigh drug loading content (DLC) of PTX alone of up to 72.3 +/- 1.7 wt % which, to our best knowledge, is among the highest level reported in literature. Moreover, the ECX NVs with the EB-CPT:PTX weight ratio of 1:2 showed remarkable combination index of 0.59 at a level of 50 % efficacy against HCT116 cells in vitro and greatly improved tumor inhibition effect in vivo compared with two clinically approved CPT- and PTX-based anticancer nanomedicines (Onivyde and Abraxane) individually and their combinations.

Automated summary

By modulating the self-assembly of drug amphiphiles EB-CPT with the anticancer drug PTX, ultrahigh quality nanovesicles (NVs) were produced with high drug loading efficiency and content. The ECX NVs with EB-CPT:PTX weight ratio of 1:2 exhibited remarkable anticancer activity against cancer cells and improved tumor inhibition effect in vivo.