Regulation of drug release performance using mixed doxorubicin-doxorubicin dimer nanoparticles as a pH-triggered drug self-delivery system

摘要

A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pHtriggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOX_(ADH) and D-DOX_(car) conjugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOX_(ADH)(D-DOX_(ADH)-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slowrelease mixed DSDS nanoparticles.