• Title/Summary/Keyword: Delivery Charge

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Bio-Derived Poly(${\gamma}$-Glutamic Acid) Nanogels as Controlled Anticancer Drug Delivery Carriers

  • Bae, Hee Ho;Cho, Mi Young;Hong, Ji Hyeon;Poo, Haryoung;Sung, Moon-Hee;Lim, Yong Taik
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1782-1789
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    • 2012
  • We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(${\gamma}$-glutamic acid) (${\gamma}$-PGA). ${\gamma}$-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated ${\gamma}$-PGA was synthesized by covalent coupling between the carboxyl groups of ${\gamma}$-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded ${\gamma}$-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated ${\gamma}$-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated ${\gamma}$-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked ${\gamma}$-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels in aqueous solution were $136.3{\pm}37.6$ nm and $-32.5{\pm}5.3$ mV, respectively. The loading amount of Dox was approximately 38.7 ${\mu}g$ per mg of ${\gamma}$-PGA nanogel. The Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1-10 mM). Through fluorescence microscopy and FACS, the cellular uptake of ${\gamma}$-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of ${\gamma}$-PGA nanogels. The bio-derived ${\gamma}$-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.

Internet Access Charging under High Quality Contents Delivery (고품질 콘텐츠 제공환경하에서 인터넷 접속료 책정방안)

  • Jung, Choong-Young
    • The Journal of the Korea Contents Association
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    • v.17 no.11
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    • pp.588-599
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    • 2017
  • This paper analyzes internet access model between ISP, CP and end users where CP uses various technologies to provide direct access to ISP owning subscribers to consume its own contents in low cost and high quality. The level of access charge depends on the competitiveness of CP market. When CP market is perfect competitive, the level of access charge is identical to that of social optimum while when CP market is monopoly, the level of access charge is influenced by the sensitivity of the contents price to access charge for CP. The dead weight loss due to monopoly market in CP can be removed by the regulation of access charge. Socially optimal access charge in monopoly market of CP is lower than that in competitive market. This is because the regulator wants to set access price to lower level to reduce welfare loss from monopoly in CP market where CP determines the price to over marginal cost.

Micro-PIV Analysis of Electro-osmotic Flow inside Microchannels (마이크로 채널 내부 전기삼투 유동에 대한 PIV유동 해석)

  • Kim Yang-Min;Lee Sang-Joon
    • Journal of the Korean Society of Visualization
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    • v.1 no.2
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    • pp.47-51
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    • 2003
  • Microfluidic chips such as lab-on-a-chip (LOC) include micro-channels for sample delivery, mixing, reaction, and separation. Pressure driven flow or electro-osmotic flow (EOF) has been usually employed to deliver bio-samples. Having some advantages of easy control, the flow characteristics of EOF in microchannels should be fully understood to effectively control the electro-osmotic pump for bio-sam-pie delivery. In this study, a micro PIV system with an epifluorescence inverted microscope and a cooled CCD was used to measure velocity fields of EOF in a glass microchannel and a PDMS microchannel. The EOF velocity fields were changed with respect to electric charge of seeding particles and microchannel materials used. The EOF has nearly uniform velocity distribution inside the microchannel when pressure gradient effect is negligible. The mean streamwise velocity is nearly proportional to the applied electric field. Glass microchannels give better repeatability in PIV results, compared with PDMS microchannels which are easy to fabricate and more suitable for PIV experiments.

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Skin Transport of Synthetic Oligodeoxynucleotide (합성 올리고데옥시뉴클레오타이드의 피부투과)

  • Lee, Young-Mi;Lee, Sung-Hee;Kim, Jae-Baek;Sohn, Dong-Hwan
    • Journal of Pharmaceutical Investigation
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    • v.25 no.4
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    • pp.347-351
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    • 1995
  • Antisense phosphorothioate oligodeoxynucleotide(PS-ODN) against $TGF-{\beta}$ was developed as scar formation inhibitor. The scar was caused collagen deposition due to overexpression of $TGF-{\beta}$ in wounded skin. The percutaneous absorption of partially modified PS-ODN(25 mer) was investigated for the purpose of its effective delivery. Though PS-ODN has high molecular weight (MW=8,000) and polyanionic charge, it was permeated through skin. The skin permeation of PS-ODN was markedly increased by the removal of stratum corneum and dermis. Moreover, the skin permeation of PS-ODN was decreased in the following order; hairless mouse skin>rat skin>human cadaver skin. Thus, PS-ODN represents a logical candidate for further evalution due to the potential for delivery into the wounded skin.

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Preparation and Mucoadhesive Test of CSA-loaded Liposomes with Different Characteristics for the Intestinal Lymphatic Delivery

  • Kim, Hyong-Ju;Lee, Chang-Moon;Lee, Yong-Bok;Lee, Ki-Young
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.6
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    • pp.516-521
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    • 2005
  • Drug delivery to the lymphatic system may be important in terms of the treatment with lymphatic involvement, such as tumor metastases and immunization. Especially, drug transport via the intestinal lymphatics after oral administration has been attracted lots of interests. The purpose of this study was to prepare cyclosporin A (CSA)-loaded liposomes, with different characteristics, and evaluate their mucoadhesivity. Three liposome preparations were formulated: cationic stearylamine liposomes (SA-Lip), anionic phosphatidylserine liposomes (PS-Lip), Polymer (chitosan)-coated liposomes (CS-Lip), and characterized. The liposome preparations were found to be spherical in shape, with PS-Lip being the smallest. The liposome preparations exhibited entrapment efficiencies in the order: PS-Lip $(52.5{\pm}2.9%)$ > SA-Lip $(48.8{\pm}3.3%)$ > CS-Lip $(41.7{\pm}4.2%)$. Finally, mucoadhesive tests were carried out using rat intestine, with SA-Lip (67%) showing the best adhesive rate of the three preparations (PS-Lip: 56%, CS-Lip: 61%). These results suggest that a positive charge on the surface of drug carriers may be an important factor for the intestinal drug delivery.

A Constitutional Review on Compensation for Medical Malpractice during Delivery (의료분쟁조정법상 의료사고보상사업의 헌법적 쟁점)

  • Cheon, Kwang-Seok
    • The Korean Society of Law and Medicine
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    • v.13 no.1
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    • pp.295-329
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    • 2012
  • A medical malpractice case requires special legal protection, considering its characteristics, such as seriousness and long term effects of its damages, medical information asymmetry between practitioners and patients, and difficulties in realization of liability. Taking the points above into consideration, Medical Malpractice Arbitration Act of 2012(MAA) has legislative intent to protect the rights of the injured from medical malpractice, while protecting the stability of medical practice by providing arbitration as an alternative dispute resolution. However, constitutional review is required for one new scheme of compensation for medical injuries during delivery, which is implemented in MAA of 2012, especially with regard to freedom to exercise occupation, property, equality under the Constitution. Two important aspects are 1. according to the law, absolute liability applies to compensation for damages during delivery without negligence of practitioners; and 2. the practitioner bears some portion of the cost, 30% in the law above. This article aims to analyze this new institution in various aspects of the Constitution, and, as a result, it does not comply with constitutional criteria.

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Different Influences of Biotinylation and PEGylation on Cationic and Anionic Proteins for Spheroid Penetration and Intracellular Uptake to Cancer Cells

  • Jung, Won Ho;You, Gayeon;Mok, Hyejung
    • Journal of Microbiology and Biotechnology
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    • v.32 no.9
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    • pp.1209-1216
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    • 2022
  • To better understand the effects of PEGylation and biotinylation on the delivery efficiency of proteins, the cationic protein lysozyme (LZ) and anionic protein bovine serum albumin (BSA) were chemically conjugated with poly(ethylene glycol) (PEG) and biotin-PEG to primary amine groups of proteins using N-hydroxysuccinimide reactions. Four types of protein conjugates were successfully prepared: PEGylated LZ (PEG-LZ), PEGylated BSA (PEG-BSA), biotin-PEG-conjugated LZ (Bio-PEG-LZ), and biotin-PEG-conjugated BSA (Bio-PEG-BSA). PEG-LZ and Bio-PEG-LZ exhibited a lower intracellular uptake than that of LZ in A549 human lung cancer cells (in a two-dimensional culture). However, Bio-PEG-BSA showed significantly improved intracellular delivery as compared to that of PEG-BSA and BSA, probably because of favorable interactions with cells via biotin receptors. For A549/fibroblast coculture spheroids, PEG-LZ and PEG-BSA exhibited significantly decreased tissue penetration as compared with that of unmodified proteins. However, Bio-PEG-BSA showed tissue penetration comparable to that of unmodified BSA. In addition, citraconlyated LZ (Cit-LZ) showed reduced spheroid penetration as compared to that of LZ, probably owing to a decrease in protein charge. Taken together, chemical conjugation of targeting ligands-PEG to anionic proteins could be a promising strategy to improve intracellular delivery and in vivo activity, whereas modifications of cationic proteins should be more delicately designed.

Study on Charge Transfer Characteristics of Self-Assembled Viologen Monolayers

  • Park Sang-Hyun;Lee Dong-Yun;Kwon Young-Soo
    • KIEE International Transactions on Electrophysics and Applications
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    • v.5C no.4
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    • pp.161-164
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    • 2005
  • Viologen has been extensively investigated in the paper because their well-behaved electrochemistry has led to their use in a variety of theses, including the electron acceptor for the electric charge delivery mediation of the devices. It was formed monolayer in QCM by self-assembly method. We could know the adsorbed mass of viologen molecules from the frequency shift. We calculated that the adsorbed mass was about 196 [$ng/cm^2$]. We studied the electron transfer property of viologen by the cyclic voltammetry among the electrochemical process so we changed an anion like 0.1 M $NaClO_4$ and $Na_3PO_4$ electrolyte solution and investigated the interrelationship between scan rate and peak current when scan rates were increased twice.

Charge Transfer Property of Self-Assembled Viologen Monolayer by Resonant Frequency Shift of QCM (수정진동자의 공진주파수 변화에 의한 Viologen 자기조립박막의 전하이동 특성)

  • Lee, Ji-Yoon;Roh, Sung-Mi;Park, Je-Won;Kwon, Young-Soo
    • Proceedings of the KIEE Conference
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    • 2007.07a
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    • pp.2020-2021
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    • 2007
  • Viologen derivative has been widely investigated because of their well-electrochemical behavior including the electron acceptor for the electric charge delivery mediation of the devices. The viologen exist in three main oxidation states, namely, $V^{2+}{\rightleftarrows}V^{{\cdot}+}{\rightleftarrows}V^0$. These redox reactions are highly reversible and can be cycled many times without significant side reaction. In this paper, we determined the time dependence to resonant frequency shift of QCM during self-assembly process and the electrochemical behavior of the self-assembled viologen monolayers by electrochemical QCM method. The redox reactions of viologen were highly reversible and the EQCM has been employed to monitor the electrochemically induced adsorption of SAMs during the redox reactions.

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Calcitonin Transport through Skin Using Iontophoresis

  • Kim, Kyung-Min;Oh, Seaung-Youl
    • Journal of Pharmaceutical Investigation
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    • v.41 no.1
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    • pp.9-17
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    • 2011
  • The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).