title: Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.
abstract: This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging.
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", 15310 Aghia Paraskevi Attikis, Greece. Electronic address: elefth@chem.demokritos.gr.
authors.forename: Eleni K
authors.initials: EK
authors.lastname: Efthimiadou
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", 15310 Aghia Paraskevi Attikis, Greece; Materials Science Department, School of Natural Sciences, University of Patras, 26 500 Patras, Greece. Electronic address: ctapeinos@gmail.com.
authors.forename: Christos
authors.initials: C
authors.lastname: Tapeinos
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", 15310 Aghia Paraskevi Attikis, Greece. Electronic address: alexchat@ims.demokritos.gr.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Chatzipavlidis
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", 15310 Aghia Paraskevi Attikis, Greece. Electronic address: nboukos@ims.demokritos.gr.
authors.forename: Nikos
authors.initials: N
authors.lastname: Boukos
authors.affiliation: Department of Medical Instruments Technology, Technological Educational Institute, GR 122 10 Athens, Greece. Electronic address: efragogeorgi@gmail.com.
authors.forename: Eirini
authors.initials: E
authors.lastname: Fragogeorgi
authors.affiliation: Department of Medical Instruments Technology, Technological Educational Institute, GR 122 10 Athens, Greece. Electronic address: shermus1989@yahoo.gr.
authors.forename: Lazaros
authors.initials: L
authors.lastname: Palamaris
authors.affiliation: Department of Medical Instruments Technology, Technological Educational Institute, GR 122 10 Athens, Greece. Electronic address: gloudos@teiath.gr.
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", 15310 Aghia Paraskevi Attikis, Greece. Electronic address: gkordas@ims.demokritos.gr.
authors.forename: George
authors.initials: G
authors.lastname: Kordas
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D060526:Magnetic Fields; D008280:Magnetics; D051379:Mice; D008863:Microspheres; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry; D014018:Tissue Distribution; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000179:Acrylates; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D014753:Vinyl Compounds; D004317:Doxorubicin; D019904:Polymethyl Methacrylate; C004985:divinyl benzene; C036658:acrylic acid
keywords: Biodistribution; Dox release; Hollow microspheres; Hyperthermia; In vivo imaging; Radiolabeling; Stimuli responsive