Design of pH/reduction dual-responsive nanoparticles as drug delivery system for DOX: Modulating controlled release behavior with bimodal drug-loading

Abstract

pH/Reduction dual-responsive P(FPA-co-PEGMA-co-MAA) (PFPM) nanoparticles were designed for tumor-specific intracellular triggered release of anticancer drug DOX by emulsion copolymerization of 4-formylphenyl acrylate (FPA), methacrylic acid (MAA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA), with N,N-bis(acryloyl)cystamine (BACy) as crosslinker. Then three drug delivery systems (DDSs) with average hydrodynamic diameter around 200nm and drug-loading capacity (DLC) of >35% were obtained via the noncovalent interaction of DOX with the carboxyl and aldehyde groups in MAA and FPA units, covalently conjugating DOX onto the FPA units via acid-labile imine bond, or both the two modes. The in vitro release profiles showed that all the three DDSs exhibited good tumor intracellular triggered release characteristic whitout burst release. And the bimodal drug-loaded one (DOX/PFPM_C+N), which had the highest DLC of >54%, possessed the middle drug release rate, faster than the one via covalent conjugation (DOX/PFPM_C) but slower than the one via noncovalent interaction (DOX/PFPM_N). The results demonstrated that the controlled release behavior of such functional nanoparticles could be tailored with drug-loading modes.

Keywords: Anti-cancer drug; Bimodal drug-loading; Intracellular triggered release; Modulating controlled release; Polymer nanoparticles.