What is it about?
The aim of this study was the design and development of a novel de novo drug delivery systemfor cancer chemotherapy. For this purpose, chitosan (CS) functionalized using phthalic anhydride followed by 4-cyano, 4- [(phenylcarbothioyl) sulfanyl] pentanoic acid as a chain transfer agent (CTA) to afford CS-CTA macroinitiator. The synthesized CS-CTA macroinitiator was then copolymerized with methacrylic acid (MAA) monomer using reversible addition–fragmentation chain transfer (RAFT) polymerization technique to produce chitosan-graftpoly( methacrylic acid) (CS-g-PMAA) graft copolymer. Afterward, graphene oxide (GO) nanosheets were incorporated into the synthesized copolymer through the physical interactions. The CS-g-PMAA/GO nanocomposite was loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The biocompatibility, DOXloading capacity, and pH dependent drug release behavior of the developed nanocomposite were also investigated. As the experimental results, as well as superior biological and physicochemical features of CS and GO, weenvision that the developed CS-g-PMAA/GO nanocomposite may be applied as de novo drug delivery nanosystem for cancer chemotherapy.
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Why is it important?
A novel pH-responsive drug delivery nanosystemwas developed for chemotherapy of solid tumors through the conjugation of chitosangrafted- poly(methacrylic acid) with graphene oxide (CS-g-PMAA/GO) followed by loading ofDOX as amodel anticancer drug
Perspectives
A novel pH-responsive drug delivery nanosystemwas developed for chemotherapy of solid tumors through the conjugation of chitosangrafted- poly(methacrylic acid) with graphene oxide (CS-g-PMAA/GO) followed by loading ofDOX as amodel anticancer drug. In vitro cytotoxic study using MTT assay revealed that the CS-g-PMAA/GO has excellent biocompatibility even at high concentrations that qualified it as drug delivery nanosystem. The developed CS-g-PMAA/GO nanocomposite exhibited excellent drug loading and encapsulation efficiencies (93.8 and 78.6%, respectively). The DOX loaded nanosystem exhibited pHresponsive drug release profile mainly due to presence of PMAA segment as a pH-responsive biopolymer. In detail, the developed nanosystem showed the highest drug release values at pH 4, and at physiological condition (pH 7.4 and temperature of 37 °C) negligible drug release behavior was observed. MMT assay results revealed that free DOX has better performance in killing of cancer cells than those of the developed DOX-loaded CS-g-PMAA/GO nanocomposite. However, due to physicochemical as well as biological issues the use of free DOX is not recommended. In conclusion, formulated anticancer drugs lead to prolonged release profiles, favorable biodistribution, higher therapeutic outcomes and minimizing the side effects of the drug.
Farideh Mahmoodzadeh
Payame nour university
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This page is a summary of: Chitosan- grafted -poly(methacrylic acid)/graphene oxide nanocomposite as a pH-responsive de novo cancer chemotherapy nanosystem, International Journal of Biological Macromolecules, July 2018, Elsevier,
DOI: 10.1016/j.ijbiomac.2018.07.036.
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