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Poloxamer 407 Hydrogels for Intravesical Instillation to Mouse Bladder: Gel-Forming Capacity and Retention Performance

  • Kim, Sang Hyun;Kim, Sung Rae;Yoon, Ho Yub;Chang, In Ho;Whang, Young Mi;Cho, Min Ji;Kim, Myeong Joo;Kim, Soo Yeon;Lee, Sang Jin;Choi, Young Wook
    • 대한비뇨기종양학회지
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    • 제15권3호
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    • pp.178-186
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    • 2017
  • Purpose: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. Materials and Methods: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). Results: P407Gels showed a thermo-reversible phase transition at $4^{\circ}C$ (refrigerated; sol) and $37^{\circ}C$ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately $10^{\circ}C-20^{\circ}C$, 12-30 seconds, and 12-35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship ($r^2=0.988$). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution (<1 hour), even though periodic urination occurred in the mice. Conclusions: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

Liposomes for Solubilization and Delivery of Curcumin into Leukemia Cells

  • Jang, Rae-Sung;Kim, Eun-Joong;Suh, Min-Sung;Shim, Ga-Yong;Shim, Chang-Koo;Oh, Yu-Kyoung
    • Journal of Pharmaceutical Investigation
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    • 제36권5호
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    • pp.293-297
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    • 2006
  • Curcumin is a phytochemical compound with anticancer activity. Although curcumin has substantial pharmacological effect against various cancers, the low solubility of curcumin has hindered its development. For an organic solvent-free injectable formulation, we encapsulated curcumin in various liposomes. Due to its lipophilic property, curcumin was placed in the membrane region of liposomes. Curcumin was stably encapsulated in all formulations tested in this study. The cellular uptake of curcumin delivered in liposomal formulations or free form was measured in K562 human leukemia cell lines using a flow cytometry and MTT viability assay, respectively. Although all the liposomes could solubilize curcumin, the cellular levels and the anticancer effects of liposomal curcumin varied with the composition of liposomes. Moreover, liposomal curcumin down-regulated the expression of Notch-1, the molecule involved in the carcinogenesis, to the similar extent to free curcumin dissolved in dimethyl sulfoxide. These results warrant the development of liposomal curcumin as an injectable formulation for leukemia treatment.

Energy-efficient full-duplex UAV relaying networks: Trajectory design for channel-model-free scenarios

  • Qi, Nan;Wang, Wei;Ye, Diliao;Wang, Mei;Tsiftsis, Theodoros A.;Yao, Rugui
    • ETRI Journal
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    • 제43권3호
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    • pp.436-446
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    • 2021
  • In this paper, we propose an energy-efficient unmanned aerial vehicle (UAV) relaying network. In this network, the channels between UAVs and ground transceivers are model-free. A UAV acting as a flying relay explores better channels to assist in efficient data delivery between two ground nodes. The full-duplex relaying mode is applied for potential energy efficiency (EE) improvements. With the genetic algorithm, we manage to optimize the UAV trajectory for any arbitrary radio map scenario. Numerical results demonstrate that compared to other schemes (eg, fixed trajectory/speed policies), the proposed algorithm performs better in terms of EE. Additionally, the impact of self-interference on average EE is also investigated.

In Vivo Protein Transduction: Delivery of PEP-1-SOD1 Fusion Protein into Myocardium Efficiently Protects against Ischemic Insult

  • Zhang, You-en;Wang, Jia-ning;Tang, Jun-ming;Guo, Ling-yun;Yang, Jian-ye;Huang, Yong-zhang;Tan, Yan;Fu, Shou-zhi;Kong, Xia;Zheng, Fei
    • Molecules and Cells
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    • 제27권2호
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    • pp.159-166
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    • 2009
  • Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

Efficiency of occlusal and interproximal adjustments in CAD-CAM manufactured single implant crowns - cast-free vs 3D printed cast-based

  • Graf, Tobias;Guth, Jan-Frederik;Diegritz, Christian;Liebermann, Anja;Schweiger, Josef;Schubert, Oliver
    • The Journal of Advanced Prosthodontics
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    • 제13권6호
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    • pp.351-360
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    • 2021
  • PURPOSE. The aim of this study was to evaluate the efficiency of occlusal and interproximal adjustments of single implant crowns (SIC), comparing a digital cast-free approach (CF) and a protocol using 3D printed casts (PC). MATERIALS AND METHODS. A titanium implant was inserted at position of lower right first molar in a typodont. The implant position was scanned using an intraoral scanner and SICs were fabricated accordingly. Ten crowns (CF; n = 10) were subject to a digital cast-free workflow without any labside occlusal and interproximal modifications. Ten other identical crowns (PC) were adjusted to 3D printed casts before delivery. All crowns were then adapted to the testing model, simulating chair-side adjustments during clinical placement. Adjustment time, quantity of adjustments, and contact relationship were assessed. Data were analyzed using SPSS software (P < .05). RESULTS. Median and interquartile range (IQR) of clinical adjustment time was 02:44 (IQR 00:45) minutes in group CF and 01:46 (IQR 00:21) minutes in group PC. Laboratory and clinical adjustment time in group PC was 04:25 (IQR 00:59) minutes in total. Mean and standard deviation (±SD) of root mean squared error (RMSE) of quantity of clinical adjustments was 45 ± 7 ㎛ in group CF and 34 ± 6 ㎛ in group PC. RMSE of total adjustments was 61 ± 11 ㎛ in group PC. Quality of occlusal contacts was better in group CF. CONCLUSION. Time effort for clinical adjustments was higher in the cast-free protocol, whereas quantity of modifications was lower, and the occlusal contact relationship was found more favourable.

이트라코나졸 마이크로스폰지의 약물 전달 시스템: 제조, 특성 및 방출 연구 (The Microsponge Delivery System of Itraconazole: Preparation, Characterization and Release Studies)

  • 조영호;이종화;김학형;이계원
    • KSBB Journal
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    • 제26권3호
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    • pp.217-222
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    • 2011
  • Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. To improve the oral absorption and dissolution of poorly water-soluble itraconazole, microsponge system composed of $Eudragit^{(R)}$ E100 and polyvinyl alcohol(PVA) formulated by quasi-emulsion solvent diffusion method, and its physicochemical properties and pharmacokinetic parameters of itraconazole were studied. The microsponge of itraconazole were discrete free flowing micro sized particles with perforated orange peel like morphology as visualized by scanning electron microscope (SEM). Results showed that the drug loading efficiency, production yield, and particle size of itraconazole microsponge were affected by drug to polymer ratio, the volume of internal phase containing methylene chloride, stirring rate and the concentration of PVA used. Also, the results showed that the dissolution rate of itraconazole from the microsponges was affected by drug to polymer ratio. In other words, the release rate of itraconazole from microsponges was increased from at least 27.43% to 64.72% after 2 h. The kinetics of dissolution mechanism showed that the dissolution data followed Korsmeyer-Peppas model. Therefore, these results suggest that microsponge system can be useful for the oral delivery of itraconazole by manipulating the release profile.

온라인 쇼핑몰에서의 고객 감동경험 고찰 (Exploring customer delight experiences in online shopping malls)

  • 박경애;허순임
    • 한국생활과학회지
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    • 제22권2호
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    • pp.301-313
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    • 2013
  • Though customer delight is becoming one of the most important marketing key words, research in a retail setting is limited. With the dramatic growth of online retail shopping, this study explored customer delight experiences in online shopping malls by identifying the delight elements and analyzing the elements by online purchase steps. A total of 124 delight experiences collected from an unstructured questionnaire were content-analyzed. Delight elements in online shopping were categorized into service, product, price, delivery, package, and shopping mall operation in that order. Service related elements including free gifts and letters, recovery efforts for service failure, kind employees, and easy return were most frequently observed. Delights were experienced at the product receiving point, the prior-to-purchase point, the order-to-delivery point, and the post-purchase point in that order. The results revealed that customer delights in online shopping were experienced in various purchase steps by various marketing elements. Based on the results the study provided research propositions exploring the effects of expectation vs surprise, monetary vs non-monetary/emotional benefits/rewards, and core marketing elements vs augmented services on delight experiences.

Copolymerization of N-Vinyl Pyrrolidone with Functionalized Vinyl Monomers: Synthesis, Characterization and Reactivity Relationships

  • Vijaykumar, S.;Prasannkumar, S.;Sherigara, B.S.;Shelke, N.B.;Aminabhavi, Tejraj M.;Reddy, B.S.R.
    • Macromolecular Research
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    • 제17권12호
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    • pp.1003-1009
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    • 2009
  • Copolymers of N-vinylpyrrolidone (NVP) comonomer with styrene (St), hydroxypropyl methacrylate (HPMA) and carboxyphenyl maleimide (CPMI) were synthesized by free radical polymerization using 2,2'-azobisisobutyronitrile (AIBN) initiator in 1,4-dioxane solvent. The copolymers formed were characterized by FTIR, $^1H$ NMR and $^{13}C$ NMR techniques and their thermal properties were studied by DSC and TGA. Copolymer composition was determined by $^1H$ NMR and/or by elemental analysis and monomer reactivity ratios (MRR) were estimated by the linear methods of Kelen-Tudos (K-T) and extended Kelen-Tudos (EK-T) and the non-linear approach. Copolymers of St and HPMA with NVP formed blocks of one of the monomer units, whereas alternating copolymers were obtained in CPMI-NVP, depending upon the side chain substitution. The MRR values are discussed in terms of monomer structural properties such as electronegativity and electron delocalization. The sequence distribution of monomers in the copolymers was studied by statistical method based on the average reactivity ratios obtained by EK-T method.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  • Kim, Jae Ho;Jenrow, Kenneth A.;Brown, Stephen L.
    • Radiation Oncology Journal
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    • 제32권3호
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    • pp.103-115
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    • 2014
  • To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

CISG상 권리부적합에 대한 매수인의 구제권에 관한 연구 (A Study on the Buyer's Remedies in respect of Defects in Title under CISG)

  • 민주희
    • 무역상무연구
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    • 제61권
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    • pp.3-28
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    • 2014
  • This study describes the buyer's remedies regarding defects in title under CISG. Although CISG stipulates the seller's liability for the delivery of conforming goods physically at Art. 35 and legally at Art. 41 and Art. 42 respectively, the buyer's remedies are not distinguished between non-conformity governed by Art. 35 and defects in title governed by Art. 41 and Art. 42. If the seller does not fulfill his obligation under Art. 41 and Art. 42 to deliver goods which are free from third party claims, the buyer should pay attention to which remedies are available under CISG. Under CISG, for defects in title in the delivered goods, the buyer is entitled to require performance in Art. 46 (1) unless he has resorted to a remedy which is inconsistent with this requirement, to declare the contract avoided by strictly limiting the situation in which the failure by the seller to perform his obligation amounts to a fundamental breach of contract in Art. 49, to claim damages in Art. 74, and to suspend the performance of his obligation where it becomes apparent that the seller will not perform a substantial part of his obligation in Art. 71 (1). Unlike Art. 35 non-conformity, the buyer may not require delivery of substitute goods under Art. 46 (2), claim repair under Art. 46 (3), and declare price reduction for title defects under Art. 50.

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