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BÁO CÁO KẾT QUẢ NGHIÊN CỨU KHOA HỌC, CÔNG NGHÊÊ VÀ ĐÀO TẠO OVERVIEW OF SCIENTIFIC RESEARCH, TECHNOLOGY AND TRAINING Nguyễn Văn Cường Đại học Công nghiệp Tp HCM Research interest Polymeric micelles for drug delivery Introduction- Background Current therapies therapies for for cancer cancer Current Chemotherapy Radiation Chemotherapy –– aa common common therapy therapy Chemotherapy in breast breast cancer cancer in Enter Reach Anti-cancer drugs Blood stream Most parts of body Kill Surgery Hormone therapy Disrupt Cancer cells proliferate or migrate Targeted therapy Used to treat all stages of breast cancer Used before and after surgery Combine with other therapies Introduction- Background Drugs alone diffuse in Drug Delivery for cancer treatment and out the tumor blood vessels Nanocarriers reach tumors via the enhanced permeability and retention (EPR) effect Ligands grafted at the surface of nanocarriers bind to receptors Polymeric micelles for drug delivery Research structure Polymeric nanoparticle for drug delivery Linear Polymeric micelles for drug delivery N,N'-dicyclohexylcarbodiimide (DCC) 4-Dimethylaminopyridine (DMAP) Poly(ethylene glycol) (PEG) Poly(ε-caprolactone) (PCL) Synthesis of triblock copolymer Polymeric nanoparticle for drug delivery Linear Polymeric micelles for drug delivery Self-assembly Block copolymers Poly(ε-caprolactone) (PCL) Nanocarriers Poly(ethylene glycol) (PEG) Publication Journal of Nanoscience and Nanotechnology 2008 (SCI, IF = 1,56) Journal of Applied Polymer Science, 2010 (SCI, IF= 1,67 ) Doxorubicin (DOX) Journal of Nanoscience and Nanotechnology, 2011 (SCI, IF =1,56) Advances In Natural Sciences-Nanoscience and Nanotechnology, 2010 (SCIE, IF =1,56) Polymers, 2016 (SCIE, IF = 3.681) (Accepted 8/2016) Polymeric nanoparticle for drug delivery Animal study of DOX-loaded Linear micelles Treated with micellar DOX Treated with free DOX Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent Polymeric micelles for drug delivery Ligand-star-shaped copolymers Shape of nanoparticle by AFM image N,N'-dicyclohexylcarbodiimide (DCC) 4-Dimethylaminopyridine (DMAP) p-nitrophenyl chloroformate (p-NPC) Dicholoromethane (DCM) Synthesis of folic-grafted star shaped copolymer Folic-star-shaped copolymers Nanocarriers Caveolae-mediated endocytosis FR-mediated endocytosis Plasma membrane Caveolin An Endosome A Caveosome Pathway of Nanocarriers into cells Journal of Nanoscience and Nanotechnology, 2011 (SCI, IF = 1,56) Journal of Biomaterials Science, Polymer Ed , 2011 (SCI, IF = 1,64) Journal of Materials Chemistry, 2012 (SCI, IF = 6.62, Citation = 43) Polymers, 2014 (SCIE, IF = 3.681) , FOL : Folic acid , FR: Folate receptor : Doxorubicin : Caveolae Polymeric micelles for drug delivery Doxorubicin released from Polymeric Micelles In-vitro Dox released from star-shaped FOL-PEG-PCL micelles Polymeric micelles for drug delivery In-vitro Cytotoxicity DOX-Loaded FOL-PEG-PCL Micelle IC50 IC50 In vitro cytotoxicity of free DOX and DOX-loaded star-shaped FOL-PEGPCL micelle in human MCF-7 (a) and MCF-7/adr (b) breast cancer cells 12 Polymeric micelles for drug delivery Confocal Image of DOX-Loaded FOL-PEG-PCL Micelle in MCF-7 Cells 13 Polymeric micelles for drug delivery Overall Discussion Characteristics of prepared copolymeric micelles Sample EC36E (Linear) PCL100-PEEP50 Mn,nmr Micellar Micellar size size (nm)a (nm)b CMC DLE (%) DLC (%) (mg/mL) 13,700 18,945 5.6×10-3 24×10-3 40.2 150.0 50.5 156.1 26.4 55.2 3.7 4.1 15,833 62.5×10-3 110.5 148.2 90 13 (Star-shape) FOL-PEG-PCL (Star-shape) a Micelles before DOX-loading (average size with ten measurements); DLE: Drug loading efficiency; DLC: Drug loading content b Micelles after DOX-loading; NA: not available 14 Polymeric micelles for drug delivery Current study and future direction Theranostic therapy Targeting drug delivery combined with imaging agent 2Q-MEH: an imaging agent Theranostic is a combination of diagnostic and therapy 15 Preliminary Results Blank 10 µg 20 µg Preparation of 2QMEH-loaded PEG-PCL micelles 40 µg PEG-PCL micelles before and after loading 2Q-MEH 2Q-MEH: an imaging agent a) 2QMEH loaded micelles under visible light 2QMEH loaded micelles under UVlight Transparent Yellow color 2Q-MEH loaded micelles under visible light (a) and under UV-light (b) 16 Nanomaterial for wastewater treatment Suspension Nanocomposite with magnetic properties: - Magnetic Hydroxyapatite - Magnetic CNT nanocomposite - Magnetic Chitosan-PAA/Fe3O4 Separate by gravity Separate by an external magnet Preparation of photocatalyst based on metallic nanomaterials with magnetic properties: - Core-shell magnetic metal-doped ZnO nanoparticle - Magnetic nanocomposite of chitosan/metalZnO and ZnO Journal of Nano Research, 2015 (SCIE, IF = 0.49) Advances In Natural Sciences-Nanoscience and Nanotechnology, 2014 (SCIE, IF = 1,581) The Scientific World Journal, 2014 (Scopus) 17 Research and training output 60 scientific publications and 01 book chapter: SCI, 11 SCIE, ISI, Scopus, 28 domestic article and conference papers Projects PI of IUH-Project (2012-2013 and 2015-2016) Member of 02 IUH-Project (2013-2014 and 2014-2015) Member of MOIT–Project (2013-2015) Member of Nafosted Project (2013-2015) typical articles 18 Author H-index = 10 No Article Citation Targeted delivery of doxorubicin to human breast cancers by folate-decorated starshaped PEG-PCL micelle 43 Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer 32 Nano-sized micelles of block copolymers of methoxy poly(ethylene glycol)-poly(εcaprolactone)-graft-2-hydroxyethyl cellulose for doxorubicin delivery 29 Synthesis and characterization of PEG-PCL-PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer 22 Overcoming multidrug resistance of breast cancer cells by the micellar doxorubicin nanoparticles of mPEG-PCL-graft-cellulose 19 Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application 18 Molecular Targeting of Liposomal nano-particles to Lymphatic System 17 Recent Development in Nano-sized Dosage Forms of Plant Alkaloid CamptothecinDerived Drugs 15 Doxorubicin-loaded nanosized micelles of a star-shaped poly(ε-caprolactone)polyphosphoester block copolymer for treatment of human breast cancer 15 10 Recent advances in pharmacokinetics of polymeric excipients used in nanosized anti-cancer drugs 15 19 Future plans Polymeric nanopartilce for drug delivery for cancer treatment Expansion to other polymeric micelles Dual-targeting drug delivery system for cancer treatment Combination of chemotherapy and diagnostic Animal test for prepared drug delivery system Biomaterial membrane Fabricate high porous membrane for wound healing application Porous membrane with growth factor and anti-bacterial agents Nanomaterial for wastewater treatment Development of highly effective nanomaterials Nanomaterial properties impact wastewater treatment process (Composition, form, size, shape) Pilot scale of using nanomaterial for wastewater treatment The fate of nanomaterial discharged in environment 20