1,721,047 research outputs found
Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis
No full textAn autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ)-Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio)propionyl hydrazide (PDPH)-poly(ethylene glycol)-N-hydroxysuccinimide (PDPH-PEG-NHS). The successful synthesis of TCZ-ALD conjugate is corroborated by 1H NMR, the purpald assay, mass spectrometry (MS), and high performance liquid chromatography (HPLC). In vitro binding affinity and cell viability tests confirmed the biological activity of TCZ-ALD conjugate. Furthermore, in vivo efficacy of TCZ-ALD conjugate is confirmed by microcomputed tomography (CT), histology, and Western blot analyses for the treatment of RA. ? 2017 American Chemical Society.112sciescopu
Advanced materials and devices for medical applications
No full text[No abstract available]11Ysciescopu
Nose-to-brain delivery of hyaluronate - FG loop peptide conjugate for non-invasive hypoxic-ischemic encephalopathy therapy
No full textThe intranasal drug administration has attracted great interest as a non-invasive route allowing targeted delivery of drugs directly to the brain. However, one of the main issues in nasal drug administration is mucociliary clearance. Hyaluronate (HA) has been widely used as a mucoadhesive excipient for ocular, rectal, and vaginal delivery. Here, FG loop peptide (FGL) was conjugated to HA for improving enzymatic stability and delivery efficiency from the nose to the brain. The successful conjugation of FGL to aldehyde modified HA was confirmed by gel permeation chromatography (GPC) and H-1 nuclear magnetic resonance (NMR). The outstanding enzymatic stability of HA-FGL conjugate was also corroborated by the GPC. The HA-FGL conjugate showed enhanced binding affinity onto nasal epithelial cells. In addition, in vivo nose-to-brain delivery of HA-FGL conjugate could be visualized by using an IVIS imaging system and fluorescence microscopy. Finally, in vivo therapeutic effect of HA-FGL conjugate was successfully confirmed by histological analysis, transferase-mediated uridine 5-triphosphate-biotin nick end-labeling (TUNEL) assay, immunofluorescent staining, transmission electron microscopy (TEM), and rotarod tests in hypoxic-ischemic encephalopathy model animals.11Nsciescopu
Superior pre-osteoblast cell response of etched ultrafine-grained titanium with a controlled crystallographic orientation
Get PDFUltrafine-grained (UFG) Ti for improved mechanical performance as well as its surface modification enhancing biofunctions has attracted much attention in medical industries. Most of the studies on the surface etching of metallic biomaterials have focused on surface topography and wettability but not crystallographic orientation, i.e., texture, which influences the chemical as well as the physical properties. In this paper, the influences of texture and grain size on roughness, wettability, and pre-osteoblast cell response were investigated in vitro after HF etching treatment. The surface characteristics and cell behaviors of ultrafine, fine, and coarse-grained Ti were examined after the HF etching. The surface roughness during the etching treatment was significantly increased as the orientation angle from the basal pole was increased. The cell adhesion tendency of the rough surface was promoted. The UFG Ti substrate exhibited a higher texture energy state, rougher surface, enhanced hydrophilic wettability, and better cell adhesion and proliferation behaviors after etching than those of the coarse- and fine-grained Ti substrates. These results provide a new route for enhancing both mechanical and biological performances using etching after grain refinement of Ti. ? The Author(s) 2017.115Ysciescopu
Hyaluronate-Peanut Agglutinin Conjugates for Target-Specific Bioimaging of Colon Cancer
No full textColon cancer is one of the most common death-related cancers in the world. For treating colon cancer, it is crucial to detect and remove malignant lesions early. Here, we developed hyaluronate (HA)-peanut agglutinin (PNA) conjugates for the bioimaging of colon cancer. The HA-PNA conjugates were successfully synthesized by the coupling reaction between aldehyde-modified HA and the N-terminal amine group of PNA. For diagnostic imaging, rhodamine B (RhoB) was chemically conjugated onto PNA in HA-PNA conjugates. After intraluminal injection of HA-PNA-RhoB conjugates into tumor-bearing mice, small-sized colon cancers could be effectively visualized by ex vivo imaging with an in vivo imaging system (IVIS) and a two-photon microscope. With these results taken together, we could confirm the feasibility of HA-PNA-RhoB conjugates as a bioimaging agent for detecting colon cancers. ? 2017 American Chemical Society.11sciescopu
Multifunctional hyaluronate - nanoparticle hybrid systems for diagnostic, therapeutic and theranostic applications
Get PDFDiagnostic and therapeutic nanoparticles have been actively investigated for the last few decades as new platforms for biomedical applications. Despite their great versatility and potency, nanoparticles have generally required further modification with biocompatible materials such as biopolymers and synthetic polymers for in vivo administration to improve their biological functions, stability, and biocompatibility. Among a variety of natural and synthetic biomaterials, hyaluronate (HA) has been considered a promising biomolecule with which to construct nanohybrid systems, as it can enable long-term and efficient delivery of nanoparticles to target sites as well as physiological stabilization of nanoparticles by forming hydrophilic shells. In this review, we first describe various kinds of HA derivatives and their interactions with nanoparticles, and discuss how to design and develop optimal HA-nanoparticle hybrid systems for biomedical applications. Furthermore, we show several exemplary applications of HA-nanoparticle hybrid systems and provide our perspectives to their futuristic translational applications.11Nsciescopu
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Upconversion nanoparticles coated organic photovoltaics for near infrared light controlled drug delivery systems
No full textOn-demand drug delivery systems (DDSs) have been widely investigated for spatiotemporally controlled therapy with greatly improved patient compliance. However, power systems to operate the DDSs are one of the serious unmet needs constraining their further applications. Here, we report implantable organic photovoltaic cells using upconversion nanoparticles (UCNPs) for on-demand controlled drug delivery. Although skin-penetrating near infrared (NIR) light cannot be used for flexible organic photovoltaic cells, UCNPs can convert NIR light to visible light for their operation after implantation to the body. The core-shell structured UCNPs coated on flexible organic photovoltaic cells generate current flow upon NIR irradiation for triggering on-demand drug delivery from microelectromechanical system (MEMS) drug reservoirs. Gold (Au) membrane sealing the reservoirs is dissolved to AuCl4- by the applied electrical current triggering the pulsatile drug release. The successful fabrication of NIR light triggered DDS by UCNPs coated organic photovoltaic cells is confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-vis spectroscopy, photoluminescence, current density-voltage characterization, and gold thin film dissolution tests. Furthermore, on-demand model drug release tests confirm the feasibility of the new paradigm light-triggered DDS and the relevant phototherapy.11Nsciescopu
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