Doxorubicin and chrysin combination chemotherapy with novel pH-responsive poly [(lactide-co-glycolic acid)-block-methacrylic acid] nanoparticle

Abstract A novel pH-responsive poly [(lactide-co-glycolic acid)-co-methacrylic acid] [(PLGA-co-PMAA)] copolymer was synthesized through the combination of radical telomerization and ring opening polymerization method (ROP). A novel strategy to stabilize polymeric nanoparticles interacted on the terminal groups of PLGA segments in (PLGA-co-PMAA) nanoparticles with chrysin (CHS) and it was inverted to (PLGA-co-PMAA)–CHS. The studied copolymers were fully characterized by FTIR and 1HNMR spectroscopy. Nanoparticles were characterized by TEM, dynamic light scattering (DLS) and zeta potential (ξ) measurements. These polymeric nanoparticles were developed with the aim of co-delivering two different anticancer drugs Doxorubicin hydrochloride (DOX) and chrysin. In vitro cytotoxicity and antitumor effect of DOX@CHS-loaded (PLGA-co-PMAA) and DOX-loaded (CHS-PLGA-co-PMAA) were also studied through assessing the survival rate of lung cancer cell line (A549) using MTT and DAPI staining assays. Nanoparticles with homogeneous spherical morphology and an average diameter of around 100 nm were successfully obtained. The viability of human lung epithelial cancer cell lines (A549) was significantly decreased upon interaction DOX@CHS-loaded (PLGA-co-PMAA) nano-formulation. As results, we envision that the novel developed pH-responsive nanoparticle can enhance the efficacy of DOX and Chrysin combination chemotherapy effect and could be applied as an anticancer drug delivery nanosystem for further in vivo uses.