Synergistic action of doxorubicin and 7-Ethyl-10-hydroxycamptothecin polyphosphorylcholine polymer prodrug

Abstract

There are opportunities for improvements to the efficiency and toxicity of widely used cancer chemotherapy agents such as doxorubicin (DOX·HCl) and 7-Ethyl-10-hydroxycamptothecin (SN38). We developed a safe and effective combination therapy by encapsulating DOX into micelles of a zwitterionic polymer prodrug, SN38 conjugate of poly (α-azide caprolactone-co-caprolactone)-b-poly (2-methacryloyloxyethyl phosphorylcholine [P(CL/CL-g-SN38)-b-PMPC)] which was described in our previous work. The polymer prodrug micelles displayed a higher loading capacity of DOX due to the π-π stacking effect between DOX and SN38 in comparison with the micelles self-assembled by prodrug's precursor, poly(α-azide caprolactone-co-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine (P(ACL/CL)-b-PMPC). The DOX loaded prodrug micelles decelerated the release of DOX, and also prolonged its circulation. The micelles showed favorable cellular internalization by 4T1 cells. DOX loaded SN38 prodrug micelles displayed good in vitro anticancer effects owing to the synergistic action of doxorubicin and SN38 and were as effective as DOX·HCl, but with lower toxicity than DOX·HCl. Given the synergetic effects of free drug and polymer prodrug, this nanomedicine may offer a safe and effective drug delivery methodology for conventional drug formations.