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      • Controllable drug release from nano-layered hollow carrier by non-human enzyme

        Choi, Daheui,Heo, Jiwoong,Hong, Jinkee The Royal Society of Chemistry 2018 Nanoscale Vol.10 No.38

        <P>Natural polymers are widely used in biomedical applications because of their numerous effects. Especially, plant-derived natural polymers extracted from cell walls, especially wood, which is abundant, inexpensive and nontoxic to cells, have high mechanical strength to retain their turgor pressure. Plant-derived polymers are also unaffected by enzymes present in the human body, having a strong possibility to create a polymeric structure that releases drugs only exactly where needed. Therefore, plant-derived polymers are suitable for use in drug delivery systems (DDS) as they have durability with few drug leakage issues in the body. Here, to improve drug incorporation and release efficiency, we prepared a multilayer nanofilm from tannic acid (TA) and lignin extracted from plants and wood. We used a strategy involving film degradation by tannase and laccase, which are not present in humans, to depolymerize TA and lignin, respectively. The TA and lignin film was highly stable for 7 days at pH 3-7 and was readily degraded after enzyme treatment. We also observed controllable drug release and anticancer effect from the TA and lignin hollow carriers depending on enzymatic activity. By taking advantage of plant-derived polymers and non-toxic enzymatic reactions, we have demonstrated the film growth and degradation mechanism in depth and explored their use in a smart DDS with easily controlled release kinetics, which is useful as a DDS platform.</P>

      • Multilayered Controlled Drug Release Silk Fibroin Nanofilm by Manipulating Secondary Structure

        Choi, Moonhyun,Choi, Daheui,Hong, Jinkee American Chemical Society 2018 Biomacromolecules Vol.19 No.7

        <P>Many studies of drug delivery nanoplatforms have explored drug loading affinity and controlled release. The nanoplatforms can be influenced by their inherent building blocks. Natural polypeptide silk fibroin (SF) is an excellent nanoplatform material because of its high biocompatibility and unique structural properties. SF secondary structures have different properties that can be changed by external stimuli. Thus, the characterization of SF-containing platforms is strongly affected by secondary structure transformations. Structural changes can occur spontaneously, which hinders the control of structural variation in aqueous conditions. Herein, we successfully prepared a controllable secondary structure composed of SF/heparin (HEP) layer-by-layer assembled nanofilms using simple solvents (glycerol and methanol). SF in the SF/HEP nanofilms takes up than 90%, which means configurations of SF have a strong effect on the character of the nanofilms. We investigated the degradation profiles of SF/HEP nanofilms depending on their β-sheet contents and demonstrated an immediate correlation between the transformation of secondary structures inside the nanofilms and the degree of degradation of nanofilms. Finally, SF/HEP nanofilms were used as a delivery platform for incorporating the anticancer drug epirubicin (EPI). We could control the loading efficiency and release profile of EPI with various β-sheet contents of the nanofilms.</P> [FIG OMISSION]</BR>

      • Controlled surface functionality of magnetic nanoparticles by layer-by-layer assembled nano-films.

        Choi, Daheui,Son, Boram,Park, Tai Hyun,Hong, Jinkee RSC Pub 2015 Nanoscale Vol.7 No.15

        <P>Over the past several years, the preparation of functionalized nanoparticles has been aggressively pursued in order to develop desired structures, compositions, and structural order. Among the various nanoparticles, iron oxide magnetic nanoparticles (MNPs) have shown great promise because the material generated using these MNPs can be used in a variety of biomedical applications and possible bioactive functionalities. In this study, we report the development of various functionalized MNPs (F-MNPs) generated using the layer-by-layer (LbL) self-assembly method. To provide broad functional opportunities, we fabricated F-MNP bio-toolbox by using three different materials: synthetic polymers, natural polymers, and carbon materials. Each of these F-MNPs displays distinct properties, such as enhanced thickness or unique morphologies. In an effort to explore their biomedical applications, we generated basic fibroblast growth factor (bFGF)-loaded F-MNPs. The bFGF-loaded F-MNPs exhibited different release mechanisms and loading amounts, depending on the film material and composition order. Moreover, bFGF-loaded F-MNPs displayed higher biocompatibility and possessed superior proliferation properties than the bare MNPs and pure bFGF, respectively. We conclude that by simply optimizing the building materials and the nanoparticle's film composition, MNPs exhibiting various bioactive properties can be generated.</P>

      • In Vitro Osteogenic Differentiation and Antibacterial Potentials of Chalcone Derivatives

        Choi, Daheui,Park, Jin Chan,Lee, Ha Na,Moon, Ji-Hoi,Ahn, Hyo-won,Park, Kwangyong,Hong, Jinkee American Chemical Society 2018 Molecular pharmaceutics Vol.15 No.8

        <P>Chalcone derivatives have been investigated as therapeutic agents for the anticancer, antioxidant, and anti-inflammatory fields. In this study, we have synthesized four different types of chalcone derivatives and demonstrated in vitro bioactivities. We divided these derivatives into two groups of chalcones on the basis of similar substituents on the aromatic rings, and we tested cell viability and proliferation potentials, which indicated that the methoxy substituent on the A ring could enhance cytotoxicity and antiproliferation potential depending on the chalcone concentration. We also investigated osteogenic differentiation of C2C12 cells by ALP staining, the early marker for osteogenesis, which demonstrated that the chalcones could not only induce activity of BMP-2 but also inhibit the activity of noggin, a BMP antagonist. In addition, chalcone bearing hydroxyl groups at the 2-, 4-, and 6-position on the A ring inhibited <I>treptococcus mutans</I> growth, a major causative agent of dental caries. Therefore, we concluded that the chalcone derivatives synthesized in this research can be good candidates for therapeutic agents promoting bone differentiation, with an expectation of inhibiting <I>S. mutans</I>, in dentistry.</P> [FIG OMISSION]</BR>

      • Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells

        Choi, Daheui,Lee, Hwankyu,Kim, Hyun-Bum,Yang, Miso,Heo, Jiwoong,Won, Younsun,Jang, Seung Soon,Park, Jong Kuk,Son, Youngsook,Oh, Tong In,Lee, EunAh,Hong, Jinkee American Chemical Society 2017 Chemistry of materials Vol.29 No.5

        <P>Intravenous administration of mesenchymal stem cells (MSCs) has served as a clinical intervention for inflammatory diseases. Once entered to blood circulation, MSCs are exposed to a harsh environment which sharply decreases cell viability due to the fact that injected cells, being susceptible to shear stress, are subjected to the high velocities of the bloodstream and lack of proper mechanical support that keeping them in an attachment -deprived state. Here, we coated the nanofilm onto viable MSCs by depositing poly-L -lysineand hyaluronic acid molecules along with arginine-glycine-aspartic acid (RGD peptide) as building blocks to protect cells from shear stress and stabilize them in a single cell, suspension state. In this article, we found that nanofilmcoated cells showed significantly increased cell survival in vitro and in vivo, which was also supported by the activation of survival-related protein, Akt. The coated nanofilm did not interfere with the sternness of MSCs which was determined based on the colony forming unit -fibroblast (CPU-F) assay and in vitro differentiation potential. Because of the characteristics of films showing light molecular deposition density, flexibility, and looseness, application of nanofilms did not block cell migration. When the cells were administrated intravenously, the nanofilm coated MSCs not only prolonged blood circulation lifetime but also showed increased stem cell recruitment to injured tissues in the muscle injury in vivo model, due to prolonged survival. Surface modification of MSCs using nanofilms successfully modulated cell activity enabling them to survive the anoikis-inducing state, and this can provide a valuable tool to potentiate the efficacy of MSCs for in vivo cell therapy.</P>

      • Multifunctional Collagen and Hyaluronic Acid Multilayer Films on Live Mesenchymal Stem Cells

        Choi, Daheui,Park, Jaeseong,Heo, Jiwoong,Oh, Tong In,Lee, EunAh,Hong, Jinkee American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.14

        <P>Cell encapsulation has been reported to convey cytoprotective effects and to better maintain cell survival. In contrast to other studies, our report shows that the deposition of two major biomacromolecules, collagen type I (Col) and hyaluronic acid (HA), on mesenchymal stem cells (MSCs) does not entirely block the cell plasma membrane surface. Instead, a considerable amount of the surface remained uncovered or only slightly covered, as confirmed by TEM observation and by FACS analysis based on quantitative surface labeling. Despite this structure showing openness and flexibility, the multilayer Col/HA films significantly increased cell survival in the attachment deprived culture condition. In terms of stem cell characteristics, the MSCs still showed functional cell activity after film deposition, as evidenced by their colony-forming activity and in vitro osteogenic differentiation. The Col/HA multilayer films could provide a cytoprotective effect and induce osteogenic differentiation without deteriorating effect or inhibition of cellular attachment, showing that this technique can be a valuable tool for modulating stem cell activities.</P>

      • SCIESCOPUSKCI등재

        Layer-by-layer assembly of multilayer films for controlled drug release

        Choi, Daheui,Hong, Jinkee 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.1

        Drug efficacy has been improved using various methods that enhance targeting, decrease toxicity, and facilitate timely and sustained drug release. To achieve these properties, various drug loading and release platforms have been developed. Layer-by-layer (LbL) self-assembly is widely used to generate controlled and sustained drug release LbL multilayer films because it allows desired functions and structures to be obtained through a simple procedure. In this review article, we highlight controlled drug release from LbL self-assembling films with diverse release kinetics, particularly with regard to mechanisms of drug release.

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