Nanomicelles co-loaded with doxorubicin and salvianolic acid A for breast cancer chemotherapy

Abstract Background: Multi-drug delivery system based on polymer carrier is emerging for alleviating dose-limiting toxicities of first-line cytotoxic anticancer drugs such as doxorubicin (DOX) for breast cancer chemotherapy. By co-loading the premium natural antioxidant salvianolic acid A (SAA) through colloidal self-assembly of amphiphilic copolymer, we herein developed CPMSD, a complex polymeric micellar system to overcome cardiotoxicity associated with DOX.Results: Optimal formulation was obtained by DOE study and CPMSD micelles were well constructed by using mPEG-PCL for entrapment at a drug-carrier mass ratio of 1:5 and DOX-SAA mass ratio of 1:4. Molecular dynamics simulation revealed the ratiometrical co-encapsulation of SAA into the hydrophobic cavity but DOX to ball-shaped surface of micelles due to hydrophilicity. Characterization study manifested favorable biopharmaceutical properties such as small and uniform particle size, fairly high drug loading capacity, as well as good colloidal stability and controlled drug release. CPMSD maintained anticancer efficacy of DOX and the action mechanism, which did not be affected by co-administering SAA. More to the point, it was of great benefit to systemic safety and cardio-protective effect against oxidative stress injuries associated with DOX in tumor-bearing mice.Conclusions: All the findings substantiated that CPMSD would be a promising multifunctional nanosystem of DOX for breast cancer chemotherapy.