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      • Recent advances in utilization of photochemical internalization (PCI) for efficient nano carrier mediated drug delivery

        Park, Wooram,Park, Sin-Jung,Lee, Jun,Na, Kun Techno-Press 2015 Biomaterials and biomedical engineering Vol.2 No.1

        Despite recent progresses in nanoparticle-based drug delivery systems, there are still many unsolved limitations. Most of all, a major obstacle in current nanoparticle-based drug carrier is the lack of sufficient drug delivery into target cells due to various biological barriers, such as: extracellular matrix, endolysosomal barrier, and drug-resistance associated proteins. To circumvent these limitations, several research groups have utilized photochemical internalization (PCI), an extension of photodynamic therapy (PDT), in design of innovative and efficient nano-carriers drug delivery. This review presents an overview of a recent research on utilization of PCI in various fields including: anti-cancer therapy, protein delivery, and tissue engineering.

      • Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma

        Park, Wooram,Chen, Jeane,Cho, Soojeong,Park, Sin-jung,Larson, Andrew C.,Na, Kun,Kim, Dong-Hyun American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.20

        <P>Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH responsive synthetic peptides with lipid tails [octadecylamine p(API-L-Asp)(10)] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.</P>

      • Advances in the synthesis and application of nanoparticles for drug delivery : Advanced nanoparticles in drug delivery

        Park, Wooram,Na, Kun Wiley (John WileySons) 2015 Wiley interdisciplinary reviews. Nanomedicine and Vol.7 No.4

        <P>The continuous development of drug delivery systems (DDSs) has been extensively researched by the need to maximize therapeutic efficacy while minimizing undesirable side effects. Nanoparticle technology was recently shown to hold great promise for drug delivery applications in nanomedicine due to its beneficial properties, such as better encapsulation, bioavailability, control release, and lower toxic effect. Despite the great progress in nanomedicine, there remain many limitations for clinical application. To overcome these limitations, advanced nanoparticles for drug delivery have been developed to enable the spatially and temporally controlled release of drugs in response to specific stimuli at disease sites. Furthermore, the controlled self-assembly of organic and inorganic materials may enable their use in theranostic applications. This review presents an overview of a recent advanced nanoparticulate system that can be used as a potential drug delivery carrier and focuses on the potential applications of nanoparticles in various biomedical fields for human health care.</P>

      • KCI등재

        Dermatan Sulfate as a Stabilizer for Protein Stability in Poly(lactide-co-glycolide) Depot

        Wooram Park,나건 한국생물공학회 2009 Biotechnology and Bioprocess Engineering Vol.14 No.5

        Dermatan sulfate (DS), a glycosaminoglycan family, was investigated as a additive to enhance the stability of therapeutic protein with low pf value loaded in poly(lactide-co-glycolide) (PLGA) microspheres prepared by water-in-oil-in-water (W1/O/W2) method. DS maintains negative charge below pH 3.0 because of its sulfate groups, while most anionic polymer with carboxyl groups becomes neutral charge at that pH. Thus, at pH 3.0 DS can form a polyelectrolyte complex with a protein with lower pf=such as exendin-4, insulin, and human growth hormone. In order to complex with DS, bovine serum albumin (BSA) was employed as a model protein, which has low pf value (pf== 4.8). The complex prepared at pH 3.0 showed a nano-size in the range of 100~200 nm with a mono distribution. During the preparation of PLGA depot, DS concentration in water phase increases with decreasing the formation of non-covalent BSA aggregates and enhancing BSA loading efficiency. It means that DS/BSA complex system enabled to keep a stability of BSA at the water/organic interface. In an in vitro BSA release test, PLGA depot with DS exhibited a lower initial burst kinetic than only PLGA depot and continuous BSA release in almost 100% for 23 days. From the results, it was concluded that DS as an additive in PLGA depot, has a potential for the long-term delivery of therapeutic proteins with lower pf value Dermatan sulfate (DS), a glycosaminoglycan family, was investigated as a additive to enhance the stability of therapeutic protein with low pf value loaded in poly(lactide-co-glycolide) (PLGA) microspheres prepared by water-in-oil-in-water (W1/O/W2) method. DS maintains negative charge below pH 3.0 because of its sulfate groups, while most anionic polymer with carboxyl groups becomes neutral charge at that pH. Thus, at pH 3.0 DS can form a polyelectrolyte complex with a protein with lower pf=such as exendin-4, insulin, and human growth hormone. In order to complex with DS, bovine serum albumin (BSA) was employed as a model protein, which has low pf value (pf== 4.8). The complex prepared at pH 3.0 showed a nano-size in the range of 100~200 nm with a mono distribution. During the preparation of PLGA depot, DS concentration in water phase increases with decreasing the formation of non-covalent BSA aggregates and enhancing BSA loading efficiency. It means that DS/BSA complex system enabled to keep a stability of BSA at the water/organic interface. In an in vitro BSA release test, PLGA depot with DS exhibited a lower initial burst kinetic than only PLGA depot and continuous BSA release in almost 100% for 23 days. From the results, it was concluded that DS as an additive in PLGA depot, has a potential for the long-term delivery of therapeutic proteins with lower pf value

      • Recent advances in utilization of photochemical internalization (PCI) for efficient nano carrier mediated drug delivery

        Park, Wooram,Park, Sin-Jung,Lee, Jun,Na, Kun Techno-Press 2015 Biomaterials and Biomechanics in Bioengineering Vol.2 No.1

        Despite recent progresses in nanoparticle-based drug delivery systems, there are still many unsolved limitations. Most of all, a major obstacle in current nanoparticle-based drug carrier is the lack of sufficient drug delivery into target cells due to various biological barriers, such as: extracellular matrix, endolysosomal barrier, and drug-resistance associated proteins. To circumvent these limitations, several research groups have utilized photochemical internalization (PCI), an extension of photodynamic therapy (PDT), in design of innovative and efficient nano-carriers drug delivery. This review presents an overview of a recent research on utilization of PCI in various fields including: anti-cancer therapy, protein delivery, and tissue engineering.

      • KCI등재

        How Large are Local Human Capital Spillovers?: Evidence from Korea

        PARK, WOORAM Korea Development Institute 2016 KDI Journal of Economic Policy (KDI JEP) Vol.38 No.4

        This paper examines the empirical magnitude of local human capital spillovers in Korea during the 1980s and mid-1990s. Local human capital spillovers exists if plants in regions with a higher level of human capital can produce more given their own amount of input (Moretti 2004c). In particular, this paper explores an educational reform in South Korea which exogenously induced a large amount of variation in regional human capital levels. Using annually collected plant level data, I explore the effect of changes in the regional human capital levels induced by this reform on plant productivity in Korea. My results suggest that this effect is limited. I find a positive correlation between a regional level of human capital and plant productivity. However, after further addressing endogeneity using an instrumental variable, the effect of the overall regional human capital level on productivity decreases and becomes statistically insignificant.

      • SCIE

        Versatile effects of magnesium hydroxide nanoparticles in PLGA scaffold–mediated chondrogenesis

        Park, Kwang-Sook,Kim, Byoung-Ju,Lih, Eugene,Park, Wooram,Lee, Soo-Hong,Joung, Yoon Ki,Han, Dong Keun Elsevier 2018 ACTA BIOMATERIALIA Vol.73 No.-

        <P><B>Abstract</B></P> <P>Artificial scaffolds made up of various synthetic biodegradable polymers have been reported to have many advantages including cheap manufacturing, easy scale up, high mechanical strength, convenient manipulation, and molding into an unlimited variety of shapes. However, the synthetic biodegradable polymers still have the insufficiency for cartilage regeneration owing to their acidic degradation products. To reduce acidification by degradation of synthetic polymers, we incorporated magnesium hydroxide (MH) nanoparticles into porous polymer scaffold not only to effectively neutralize the acidic hydrolysate but also to minimize the structural disturbance of scaffolds. The neutralization effect of poly(D,L-lactic-co-glycolic acid; PLGA)/MH scaffold was confirmed with the maintenance of neutral pH, contrary to a PLGA scaffold with low pH. Further, the scaffolds were applied to evaluate the chondrogenic differentiation of the human bone marrow mesenchymal stem cells. In <I>in vitro</I> study, the PLGA/MH scaffold enhanced the chondrogenesis markers and reduced the calcification, compared to the PLGA scaffold. Additionally, the PLGA/MH scaffold reduced the release of inflammatory cytokines, compared to the PLGA scaffold, as the cell death decreased. Moreover, the addition of MH reduced necrotic cell death at the early stage of chondrogenic differentiation. Further, the necrotic cell death by the PLGA scaffold was mediated by cleavage of caspase-1, the so-called interleukin 1-converting enzyme, and MH alleviated it as well as nuclear factor kappa B expression. Furthermore, the PLGA/MH scaffold highly supported chondrogenic healing of rat osteochondral defect sites in <I>in vivo</I> study. Therefore, it was suggested that a synthetic polymer scaffold containing MH could be a novel healing tool to support cartilage regeneration and further treatment of orthopedic patients.</P> <P><B>Statement of Significance</B></P> <P>Synthetic polymer scaffolds have been widely utilized for tissue regeneration. However, they have a disadvantage of releasing acidic products through degradation. This paper demonstrated a novel type of synthetic polymer scaffold with pH-neutralizing ceramic nanoparticles composed of magnesium hydroxide for cartilage regeneration. This polymer showed pH-neutralization property during polymer degradation and significant enhancement of chondrogenic differentiation of mesenchymal stem cells. It reduced not only chondrogenic calcification but also release of proinflammatory cytokines. Moreover, it has an inhibitory effect on necrotic cell death, particularly caspase-1-mediated necrotic cell death (pyroptosis). In <I>in vivo</I> study, it showed higher healing rate of the damaged cartilage in a rat osteochondral defect model. We expected that this novel type of scaffold can be effectively applied to support cartilage regeneration and further treatment of orthopedic patients.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCISCIESCOPUS

        Synthetic matrix containing glucocorticoid and growth factor for chondrogenic differentiation of stem cells

        Park, Keun-Hong,Park, Wooram,Na, Kun Elsevier 2009 Journal of bioscience and bioengineering Vol.108 No.2

        <P><B>Abstract</B></P><P>With the present study the aim was to assess the efficacy of synthetic matrix as specific drug carriers carrying encapsulation of cells for the differentiation using mesenchymal stem cells (MSCs). The poly(N-isopropylacrylamide-co-vinylimidazole); p(NiPAAm-co-VI)) matrix itself, synthetic matrix, without drugs was used as the control in order to determine the effects of these materials on differentiation. MSCs obtained from rabbit bone marrow were tested as a potential cell source for tissue regeneration encapsulated in synthetic matrix, in the presence or absence of the growth factor (TGF-β1) and dexamethasone (Dex). The encapsulated with cells and synthetic matrix were transplanted into a nude mouse as an injected form and cultured for up to 8?weeks. The specific gene expression was determined by RT-PCR analysis. The amount of cartilage-associated ECM proteins was examined by Safranin-O staining. These data indicate the potential use of TGF-β1 and Dex for reconstruction of neocartilage formation. We have concluded that synthetic matrix including TGF-β 1 and Dex has useful carrier as containing inducers of chondrogenic differentiation materials in the regeneration of tissue-engineered cartilage <I>in vivo</I>.</P>

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