CCEPTED ACCEPTED MANUSCRIPT 1 Doxorubicin and Chrysin combination chemotherapy with Novel pH-responsive poly [(lactide-co-glycolic 1 acid)-block-methacrylic acid] Nanoparticle 2 Sepideh Jabbari 1 , Aliyeh Ghamkhari 2 , Yousef Javadzadeh3 , Roya Salehi 4* and Soodabeh Davaran1** 3 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, 4 Iran 5 2 Department of Chemistry, Payame Noor University, Tehran, Iran 6 3 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran 7 4 Drug Applied Research Center and Department of Medical Nanotechnology, School of Advanced Medical 8 Science, Tabriz University of Medical Sciences, Tabriz, Iran 9 10 Corresponding author 1: Roya. Salehi, Tel: +984133363161. Fax: +984133363132. Email: 11 salehiro@tbzmed.ac.ir 12 Corresponding author 2: Soodabeh Davaran, Tel: +9841 33372250-51. Fax: +9841 33372251. Email: 13 davaran@tbzmed.ac.ir 14 Abstract 15 A novel pH-responsive poly [(lactide-co-glycolic acid)-co-methacrylic acid] [(PLGA-co-PMAA)] copolymer 16 was synthesized through the combination of radical telomerization and ring opening polymerization method 17 (ROP). A novel strategy to stabilize polymeric nanoparticles interacted on the terminal groups of PLGA 18 segments in (PLGA-co-PMAA) nanoparticles with chrysin (CHS) and it was inverted to (PLGA-co-PMAA)– 19 CHS. The studied copolymers were fully characterized by FTIR and 1HNMR spectroscopy. Nanoparticles were 20 characterized by TEM, dynamic light scattering (DLS) and zeta potential (ξ) measurements. These polymeric 21 nanoparticles were developed with the aim of co-delivering two different anticancer drugs Doxorubicin 22 hydrochloride (DOX) and chrysin. In vitro cytotoxicity and antitumor effect of DOX@CHS-loaded (PLGA-co- 23 PMAA) and DOX-loaded (CHS-PLGA-co-PMAA) were also studied through assessing the survival rate of lung 24 cancer cell line (A549) using MTT and DAPI staining assays. Nanoparticles with homogeneous spherical 25 morphology and an average diameter of around 100 nm were successfully obtained. The viability of human lung 26 epithelial cancer cell lines (A549) was significantly decreased upon interaction DOX@CHS-loaded (PLGA-co- 27 PMAA) nano-formulation. 28 As results, we envision that the novel developed pH-responsive nanoparticle can enhance the efficacy of DOX 29 and Chrysin combination chemotherapy effect and could be applied as an anticancer drug delivery nanosystem 30 for further in vivo uses. 31
کلید واژگان :ROP polymerization, nanoparticle, Doxorubicin hydrochloride, Chrysin, Combination 32 chemotherap
ارزش ریالی : 600000 ریال
با پرداخت الکترونیک