• Title/Summary/Keyword: pH-sensitive release

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Pulsatile Interpenetrating Polymer Networks Hydrogels Composed of Poly(vinyl alcohol) and Poly(acrylic acid) ; Synthesis, Characterization, and its Application to Drug Delivery Systems

  • Shin, Heung-Soo;Kim, So-Yeon;Lee, Young-Moo
    • Proceedings of the KOSOMBE Conference
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    • v.1996 no.11
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    • pp.281-285
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    • 1996
  • Pulsatile swelling behaviors and their application to drug delivery system were studied by using interpenetrating polymer networks(IPN) hydrogels constructed with poly(vinyl alcohol) and poly(acrylic acid). The PVA/PAAc IPNs hydrogels were symthesized by UV irradiation tallowed by repetitive freezing and thawing method. These hydrogels showed pH and temperature sensitive swelling behaviors. From the release experiment, the release amount of model drug incorporated into these hydrogels showed pulsatile patterns. Permeability coefficients obtained by various solutes differed in response to changes of permeation conditions.

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Protective Effects on A2Kb Transgenic Mice That Were Immunized with Hepatitis B Virus X Antigen Peptides by the Activation of CD8+ T Cells; XEP-3 Specific CTL Responses in the in vitro Culture (B형 간염 바이러스 X 항원을 면역한 A2Kb Transgenic Mice에서 CD8+ T Cell의 활성화에 의한 X 항원 표현 재조합 Vaccinia Virus에 대한 방어 효과; in vitro 배양을 통한 XEP-3 특이적인 CTL의 반응)

  • Hwang, Yu Kyeong;Kim, Hyung-Il;Kim, Nam Kyung;Park, Jung Min;Cheong, Hong Seok
    • IMMUNE NETWORK
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    • v.2 no.1
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    • pp.41-48
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    • 2002
  • Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

Bioinspired Polymers that Control Intracellular Drug Delivery

  • Allan S. Hoffman;Patrick S. Stayton;Oliver-Press;Niren-Murthy;Chantal A. Lackey;Charles-Cheung;Fiona-Black;Jean Campbell;Nelson Fausto;Themis R. Kyriakides;Paul-Bornstein
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.6 no.4
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    • pp.205-212
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    • 2001
  • One of the important characteristics of biological systems os their ability to change im-portant properties in response to small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting models for the development of "smart" polymeric biomaterials with biomimetic properties. An important example of this is the protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis, then out of the endosome into the cytoplasm, and from there into the nucleus, We have designed a family of synthetic polymers whose compositions have been de-signed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic polymers are responsive to the lowered pH whinin endosomes, leading to distruption of the en-dosomal membrane and release of important biomolecular druges such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal en-zymes. In this article, we review our work on the design, synthesis and action of such smart, pH-sensitive polymers.

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Properties of Spontaneous Activity in Gastric Smooth Muscle

  • Suzuki, H.;Yamamoto, Y.;Hirst, G.D.S.
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.2
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    • pp.119-125
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    • 1999
  • Mammalian gastric smooth muscles generate spontaneous rhythmic contractions which are associated with slow oscillatory potentials (slow waves) and spike potentials. Spike potentials are blocked by organic $Ca^{2+}-antagonists,$ indicating that these result from the activation of L-type $Ca^{2+}-channel.$ However, the cellular mechanisms underlying the generation of slow wave remain unclear. Slow waves are insensitive to $Ca^{2+}-antagonists$ but are blocked by metabolic inhibitors or low temperature. Recently it has been suggested that Interstitial Cells of Cajal (ICC) serve as pacemaker cells and a slow wave reflects the coordinated behavior of both ICC and smooth muscle cells. Small segments of circular smooth muscle isolated from antrum of the guinea-pig stomach generated two types of electrical events; irregular small amplitude (1 to 7 mV) of transient depolarization and larger amplitude (20 to 30 mV) of slow depolarization (regenerative potential). Transient depolarization occurred irregularly and membrane depolarization increased their frequency. Regenerative potentials were generated rhythmically and appeared to result from summed transient depolarizations. Spike potentials, sensitive to nifedipine, were generated on the peaks of regenerative potentials. Depolarization of the membrane evoked regenerative potentials with long latencies (1 to 2 s). These potentials had long partial refractory periods (15 to 20 s). They were inhibited by low concentrations of caffeine, perhaps reflecting either depletion of $Ca^{2+}$ from SR or inhibition of InsP3 receptors, by buffering $Ca^{2+}$ to low levels with BAPTA or by depleting $Ca^{2+}$ from SR with CPA. They persisted in the presence of $Ca^{2+}-sensitive$ $Cl^--channel$ blockers, niflumic acid and DIDS or $Co^{2+},$ a non selective $Ca^{2+}-channel$ blocker. These results suggest that spontaneous activity of gastric smooth muscle results from $Ca^{2+}$ release from SR, followed by activation of $Ca^{2+}-dependent$ ion channels other than $Cl^-$ channels, with the release of $Ca^{2+}$ from SR being triggered by membrane depolarization.

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Effect of Ginseng Saponin on the Mobilization of Free Fatty Acid from Epididymal Fat Pad of Rat (인삼 Saponin이 백서부고환지방조직에서의 유리지방산동원에 미치는 효과)

  • Park C.W.;Kim M.S.
    • The Korean Journal of Pharmacology
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    • v.10 no.1 s.15
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    • pp.41-45
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    • 1974
  • The effect of ginseng saponin on the release of free fatty acid from adipose tissue was studied in vitro. 1. The mobilization of free fatty acid from intact epididymal fat pad of rat, incubated in Krebs-Ringer bicarbonate buffer (pH 7.4) contained bovine serum albumin (4 w/v%), was increased by addition of ginseng sponin (1 mg/ml). 2. The mobilization of free fatty acid from homogenate of the epididymal fat pad of rat, of which hormone-sensitive lipese system was activated by pre-incubation of intact fat pad in the presence of epinephrine, was markedly increased by addition of ginseng saponin $(0.1{\sim}1mg/ml)$. 3. It is considered that ginseng saponin potentiate the actions of epinephrine on hormone-sensitive lipase system of the adipose tissue of rat.

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Preparation and Performance Evaluation of a Zinc Oxide-Graphene Oxideloaded Chitosan-Based Thermosensitive Gel

  • Hao Huang;Rui Han;Ping-Ping Huang;Chuan-Yue Qiao;Shuang Bian;Han Xiao;Lei Ma
    • Journal of Microbiology and Biotechnology
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    • v.34 no.6
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    • pp.1229-1238
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    • 2024
  • This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxide-GrapheneOxide/Chitosan/β-Glycerophosphate (ZnO-GO/CS/β-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/β-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/β-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/β-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/β-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

Analysis of Patched Cylindrical Shells with Circumferential Through-Wall Cracks (원주방향 관통균열을 갖는 원통형 쉘 구조의 패치보강 해석)

  • Ahn, Jae-Seok;Kim, Young-Wook;Woo, Kwang-Sung
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.32 no.6A
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    • pp.411-418
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    • 2012
  • In this study, behavior of unpatched and patched cylindrical shells with through-wall cracks has been estimated using numerical experiments, and patching effect of them has been investigated according to various patching parameters. To show credibility of numerical models considered, two ways such as h- and p-methods have been adopted. Also, domain integral method and virtual crack extension method have been considered to calculate energy release rates based on linear elastic fracture mechanics. For examples, the unpatched cylindrical shells with circumferential cracks under remote tension have firstly been analyzed to show the validity of finite element modeling with h-method or p-method, and then the results have been compared with literature values published. Next, the sensitive analysis of patch repaired problems in terms of thickness of patch and adhesive, shear modulus of adhesive, composite material type of patch, crack length, etc. has been carried out.

Physicochemical Characteristics of Fe3O4 Magnetic Nanocomposites Based on Poly(N-isopropylacrylamide) for Anti-cancer Drug Delivery

  • Davaran, Soodabeh;Alimirzalu, Samira;Nejati-Koshki, Kazem;Nasrabadi, Hamid Tayefi;Akbarzadeh, Abolfazl;Khandaghi, Amir Ahmad;Abbasian, Mojtaba;Alimohammadi, Somayeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.49-54
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    • 2014
  • Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at $37^{\circ}C$. Magnetic iron oxide nanoparticles ($Fe_3O_4$) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at $40^{\circ}C$ and in acidic pH compared to that $37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

Studies on the Controlled Release Fertilizer METAP Application on Paddy Rice (1972) (수도에 대한 완효성비료 METAP의 비효시험(1972))

  • Lee, E.W.;Ahn, S.B.;Lee, M.H.;Lee, Z.Y.;Song, N.H.;Kwon, S.M.;Kim, C.Y.;Choe, B.C.;Chung, H.S.;Cho, B.O.;Lee, I.J.;Park, C.S.;Ko, C.S.;Park, K.H.;Chung, S.C.;Chung, H.S.;Lee, H.D.;Park, S.T.;Lee, H.S.;Choe, S.R.
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.13
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    • pp.107-118
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    • 1973
  • Experiments were carried out to study the effectiveness of METAP as a slow released fertilizer on the growth, grain yield and its components of paddy rice, and to compare its effects with those of single fertilizers in the fields of 3 Crop Experiment Stations and 7 provincial Offices of Rural Development. The effectiveness of METAP seems to be different according to the physical and chemical characteristics of soil, the time of application, climatic conditions, variety and cultural methods. Therefore, the experimental results obtained from the above experiment are summurized as follows: 1. When METAP was applied into sandy soil, grain yield was increased due to increase of the number of panicles, and split application of METAP was more effective than basal only. However, in the reclaimed soil, not heavily percolated soil and fertile soil, no differences were observed between MET AP and single fertilizer applied plot. 2. When a rice variety, 'TONGIL' which is sensitive to the low temperature and produce higher yield in the early transplanting, was not transplanted early and air temperature is relatively lower during the ripening stage, the percentage of ripened grains and 1,000 grains weight were not higher in the METAP applied plots than in the single fertilizer applied plots.

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Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets

  • Jiang, Tao;Li, Hui-Shan;Han, Geon Goo;Singh, Bijay;Kang, Sang-Kee;Bok, Jin-Duck;Kim, Dae-Duk;Hong, Zhong-Shan;Choi, Yun-Jaie;Cho, Chong-Su
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.739-746
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    • 2017
  • As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.