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Poly(benzyl-L-histidine)-b-Poly(ethylene glycol) Micelle Engineered for Tumor Acidic pH-Targeting, in vitro Evaluation

  • Lee, Eun-Seong;Youn, Yu-Seok
    • Bulletin of the Korean Chemical Society
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    • 제29권8호
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    • pp.1539-1544
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    • 2008
  • A polymeric micelle, based on the poly(benzyl-L-histidine)-b-poly(ethylene glycol) (polyBz-His-b-PEG) diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 $\mu$g/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

기판단위 밀봉 패키징을 위한 내압 동공열의 설계 및 강도 평가 (Design and Strength Evaluation of an Anodically Bonded Pressurized Cavity Array for Wafer-Level MEMS Packaging)

  • 강태구;조영호
    • 대한기계학회논문집A
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    • 제25권1호
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    • pp.11-15
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    • 2001
  • We present the design and strength evaluation of an anodically bonded pressurized cavity array, based on the energy release rate measured from the anodically bonded plates of two dissimilar materials. From a theoretical analysis, a simple fracture mechanics model of the pressurized cavity array has been developed. The energy release rate (ERR) of the bonded cavity with an infinite bonding length has been derived in terms of cavity pressure, cavity size, bonding length, plate size and material properties. The ERR with a finite bonding length has been evaluated from the finite element analysis performed for varying cavity and plate sizes. It is found that, for an inter-cavity bonding length greater than the half of the cavity length, the bonding strength of cavity array approaches to that of the infinite plate. For a shorter bonding length, however, the bonding strength of the cavity array is monotonically decreased with the ratio of the bonding length to the cavity length. The critical ERR of 6.21J/㎡ has been measured from anodically bonded silicon-glass plates. A set of critical pressure curves has been generated for varying cavity array sizes, and a design method of the pressurized cavity array has been developed for the failure-free wafer-level packaging of MEMS devices.

모델 스크램제트 연소기 내의 열적 질식 과정 수치 연구 (Numerical Study of Thermal Choking Process in a Model SCRamjet Combustor)

  • 이병로;문귀원;정인석;최정열
    • 한국연소학회:학술대회논문집
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    • 한국연소학회 2000년도 제21회 KOSCO SYMPOSIUM 논문집
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    • pp.83-91
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    • 2000
  • A numerical study was carried out to investigate the 'unstart' process of thermally-choked combustion in model scramjet engines. The combustion mechanism of supersonic combustor will be compared with the experimental results obtained from the T3 free-piston shock tunnel at ANU (Australian National University) and the high enthalpy supersonic wind tunnel at UT (University of Tokyo). For the numerical simulation of supersonic combustion. multi-species Navier-Stokes equations were considered. and detailed chemistry reaction mechanism of $H_2$-Air were adopted. The governing equations were solved by Roe's FDS method and LU-SGS method with MUSCL scheme. In this study. it is found that the thermal choking process could result from excessive heat release due to combustion. In detail, sufficient heat release could be generated at local region of very high temperature increased by reflection of shock waves or vortex sheets. Accordingly the flow of downstream of the combustor fell to subsonic field propagated upstream along the combustor. Sometimes the subsonic flow field propagated into isolator could generate precombustion shock waves in the isolator.

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Poly(vinyl pyrrolidone) Conjugated Lipid System for the Hydrophobic Drug Delivery

  • Lee, Hye-Yun;Yu, Seol-A;Jeong, Kwan-Ho;Kim, Young-Jin
    • Macromolecular Research
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    • 제15권6호
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    • pp.547-552
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    • 2007
  • Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

Equilibrium Thermodynamics of Chemical Reaction Coupled with Other Interfacial Reactions Such as Charge Transfer by Electron, Colligative Dissolution and Fine Dispersion: A Focus on Distinction between Chemical and Electrochemical Equilibria

  • Pyun, Su-Il;Lee, Sung-Jai;Kim, Ju-Sik
    • 전기화학회지
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    • 제11권4호
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    • pp.227-241
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    • 2008
  • This article involves a unified treatment of equilibrium thermodynamics of the chemical reaction coupled with other interfacial (phase boundary) reactions. The modified (restrictive) chemical potential ${\mu}_k^+$, such as electrochemical potential, hydrostatic-chemical (mechanochemical) potential (exceptionally in the presence of the pressure difference) and surface-chemical potential, was first introduced under the isothermal and isobaric conditions. This article then enlightened the equilibrium conditions in case where the release of chemical energy is counterbalanced by the supply of electrical energy, by the supply of hydrostatic work (exceptionally in the presence of ${\Delta}p$), and finally by the release of surface energy, respectively, at constant temperature T and pressure p in terms of the modified chemical potential ${\mu}_k^+$. Finally, this paper focussed on the difference between chemical and electrochemical equilibria based upon the fundamentals of the isothermal and isobaric equilibrium conditions described above.

만삼(蔓蔘)의 과산화수소에 의한 SK-N-MC의 세포사에 미치는 영향 (Protection of Codonopis pilosula Extract against Cell Death of SK-N-MC Neuroblastoma Cells Treated with $H_2O_2$)

  • 이선구
    • 동의생리병리학회지
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    • 제22권2호
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    • pp.328-332
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    • 2008
  • The purpose of this study was to identify the protective effect of Codonopis pilosula extract on cell death induced by $H_2O_2$ in SK-N-MC neuroblastoma cells. We measured the antioxidant effect by DPPH radical scavenging analysis, BSA analyssis and examined the cell viability by crystal violet and cytochrome C, Bax, Bcl-2, p53, p21 by using Western blot analysis. Codonopis pilosula extract scavenged DPPH radical in a dose-dependent manner and shown direct free radical scavenging effect, suggested that Codonopis pilosula extract have antioxidant effect in vitro. Treatment of cells with hydrogen peroxide, a reactive oxygen species, was to induce cell death and pretreatment with Codonopis pilosula extract attenuated the occurrence of $H_2O_2-induced$ cell death. To elucidate the protective mechanisms of action of Codonopis pilosula extract, Western blot analyses for Bcl-2 and Bax expression and cytochrome c release were carried out. Pretreatment with Codonopis pilosula extract induced the expression of Bcl-2 and suppressed the release of cytochrome c and Bax into the cytosol, thereby arresting $H_2O_2-induced$ apoptotic cell death. Especially p21 and p53 were decreased prior to $H_2O_2$ treatment. These results suggest that Codonopis pilosula extract is associated with the cell cycle and anti-apoptotic cell death.

Methanolic Extract of Turmeric (Curcuma longa L.) Enhanced the Lipolysis by Up-regulation of Lipase mRNA Expression in Differentiated 3T3-L1 Adipocytes

  • Lee, Jeong-Min;Jun, Woo-Jin
    • Food Science and Biotechnology
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    • 제18권6호
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    • pp.1500-1504
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    • 2009
  • Effects of methanol extract from turmeric (Curcuma longa L.) (CME) on underlying mechanisms of lipolysis were investigated in 3T3-L1 adipocytes. Compared to the control, lipid accumulation with 72 hr treatment of CME at the concentration $20\;{\mu}g/mL$ was significantly decreased by 19.9% as quantified by Oil red O dye. Intracellular triglyceride (TG) content was also lowered by 19.3%. To determine the mechanism for TG content reduction, glycerol release level was measured. Incubation of 3T3-L1 adipocytes with 15 and $20\;{\mu}g/mL$ of CME significantly elevated the level of free glycerol released into the cultured medium by 20.4 and 28.6%, respectively. In subsequent measurements using quantitative real-time polymerase chain reaction (PCR), mRNA levels of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) were significantly increased by 21.2 and 24.9%, respectively, at the concentration $20\;{\mu}g/mL$. Results indicated that CME stimulated lipolysis through induction of HSL and ATGL mRNA expressions, resulting in increased glycerol release.

Kainate-induced Elevations of Intracellular $Ca^{2+}$ and Extracellular Glutamate are Partially Decreased by NMDA Receptor Antagonists in Cultured Cerebellar Granule Neurons

  • Oh, Seikwan;Shogo-Tokuyama;Patrick P.McCaslin
    • Archives of Pharmacal Research
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    • 제18권6호
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    • pp.391-395
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    • 1995
  • Several lines of evidence indicate that physiological activity of N-methyl-D-aspartate (NMDA) receptor was blocked by physiological concentration of $Mg^{2+}$ (1.2 mM). However, the activity of NMDA receptor may not be blocked totally with this concentration of $Mg^{2+}$ under elevated membrane potential by kainate. Here, we described the effect of $Mg^{2+}$ on NMDA receptor and how much of NMDA receptor functions could be activated by kainate. Effects of NMDA receptor antagonist on kainate-induced elevation of intracellualr $Ca^{2+}$ levels $([Ca^{2+}]_i)$ and extracellular glutamate level were examined in cultured rat cerebellar granule neurons. kainate-induced elevation of $([Ca^{2+}]_i)$ was not affected by physiological concentration of $Mg^{2+}$. Kainate-induced NMDA-induced elevation was blocked by the same concentration of $MG^{2+}$Kainate-induced elevation of [$([Ca^{2+}]_i)$ was decreased by 32% in the presence of NMDA antagonists, MK-801 and CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid), in $Mg^{2+}$ free buffer. Kainate receptor-activated gluamate release was also decreased (30%) by MK-801 or CPP. These resuts show that certain extent of elevations of intracellular $Ca^{2+}$ and extracellular glutamate by kainate is due to coativation of NMDA receptors.

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Protection of the Flowers of Prunus persica Extract from Ultraviolet B-Induced Damage of Normal Human Keratinocytes

  • Kim, Young-Ha;Yang, Hye-Eun;Kim, Jong-Ha;Heo, Moon-Young;Kim, Hyun-Pyo
    • Archives of Pharmacal Research
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    • 제23권4호
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    • pp.396-400
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    • 2000
  • For an attempt to develop safe materials protecting solar ultraviolet (UV)-induced skin damage, plant extracts were evaluated for their inhibitory activities of free radical generation and arachidonic acid/metabolites release from UVB-irradiated normal human keratinocytes. From the results of these screening procedures, the ethanol extract of the flowers of Prunus persica (Ku-35) was selected for further study. It was found that Ku-35 (100-1,000 ${u}g/m\ell$) inhibited the amount of $^{14}C$-arachidonic acid/metabolites release from UVB-irradiated keratinocytes. It was also demonstrated that Ku-35 possessed the protective activity against UV-induced cytotoxicity of keratinocytes and fibroblasts. In addition, Ku-35 was revealed to protect UVB-induced erythema formation using guinea pigs in preliminary in vivo study. All these results indicate that the flowers of P. persica extract may be beneficial for protecting UV-induced skin damage when topically applied.

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Protective Effects of a Monoclonal Antibody to a Mannose-Binding Protein of Acanthamoeba culbertsoni

  • Park, A-Young;Kang, A-Young;Jung, Suk-Yul
    • 대한의생명과학회지
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    • 제24권4호
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    • pp.435-438
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    • 2018
  • Acanthamoeba culbertsoni is the causative agent of granulomatous amoebic encephalitis (GAE), a condition that predominantly occurs in immunocompromised individuals and which is typically fatal. A mannose-binding protein (MBP) among lectins was shown to have strong A. castellanii pathogenic potential when correlated with major virulence proteins. In this study, protective effects were analyzed using the monoclonal antibody to A. culbertsoni MBP by quantification and were also compared with other free-living amoebae. For the amoebial cytotoxicity to the target cell, amoeba trophozoites were incubated with Chinese hamster ovary (CHO) cells. For the protective effects of antibodies, amoebae were pre-incubated with them for 4 h and then added to the target cells. After 24 h, the supernatants were collected and examined for host cell cytotoxicity by measuring lactate dehydrogenase (LDH) release. The cytotoxicity of A. culbertsoni to the CHO cells showed about 87.4%. When the monoclonal antibody was pre-incubated with A. culbertsoni, the amoebial cytotoxicity was remarkably decreased as shown at LDH release (1.858 absorbance), which was represented with about 49.9%. Taken together, it suggested that the monoclonal antibody against MBP be important to inhibit the cytotoxicity of A. culbertsoni trophozoites to the target cell. The antibody will be applied into an in vivo functional analysis, which would help to develop therapeutics.