• Title/Summary/Keyword: stimuli-responsive release

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Poly(Dimethylaminoethyl Methacrylate)-Based pH-Responsive Hydrogels Regulate Doxorubicin Release at Acidic Condition

  • Lee, Seung-Hun;You, Jin-Oh
    • Journal of the Korean Applied Science and Technology
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    • v.32 no.2
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    • pp.202-214
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    • 2015
  • Stimuli-responsive biomaterials that alter their function through sensing local molecular cues may enable technological advances in the fields of drug delivery, gene delivery, actuators, biosensors, and tissue engineering. In this research, pH-responsive hydrogel which is comprised of dimethylaminoethyl methacylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) was synthesized for the effective delivery of doxorubicin (Dox) to breast cancer cells. Cancer and tumor tissues show a lower extracellular pH than normal tissues. DMAEMA/HEMA hydrogels showed significant sensitivity by small pH changes and each formulation of hydrogels was examined by scanning electron microscopy, mechanical test, equilibrium mass swelling, controlled Dox release, and cytotoxicity. High swelling ratios and Dox release were obtained at low pH buffer condition, low cross-linker concentration, and high content of DMAEMA. Dox release was accelerated to 67.3% at pH 5.5 for 6-h incubation at $37^{\circ}C$, while it was limited to 13.8% at pH7.4 at the same time and temperature. Cell toxicity results to breast cancer cells indicate that pH-responsive DMAEMA/HEMA hydrogels may be used as an efficient matrix for anti-cancer drug delivery with various transporting manners. Also, pH-responsive DMAEMA/HEMA hydrogels may be useful in therapeutic treatment which is required a triggered release at low pH range such as gene delivery, ischemia, and diabetic ketoacidosis.

Application of Stimuli-responsive Chitosan Micelles for Improved Therapeutic Efficiency of Anticancer Agents (항암제의 치료 효율성을 높이기 위한 다양한 자극 응답성 물질이 개질된 키토산 마이셀의 응용성 고찰)

  • Jeong, Gyeong-Won;Park, Jun-Kyu;Nah, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.29 no.2
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    • pp.147-154
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    • 2018
  • Currently, to overcome low therapeutic efficiencies and side effects of anticancer agents, the study of drug carrier based on polymers have been consistently investigated. Although the traditional drug carrier based on polymers displayed an excellent result and significant progress, there has been a problem with the side effect and low therapeutic efficiency because of the premature drug release before reached to the targeted region by the low stability in blood stream and sustained drug release. In this review article, to improve the problem of inefficient drug release, methods were suggested, which can maximize the therapeutic efficiency by increasing the stability in the blood stream and triggering drug release at the target site by introducing a stimuli-responsive substance to the non-toxic and biocompatible natural polymer chitosan.

Chemoenzymatic Synthesis of Dual-responsive Amphiphilic Block Copolymers and Drug Release Studies

  • Chen, Peng;Li, Ya-Peng;Wang, Shu-Wei;Meng, Xin-Lei;Zhu, Ming;Wang, Jing-Yuan
    • Bulletin of the Korean Chemical Society
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    • v.34 no.6
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    • pp.1800-1808
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    • 2013
  • Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.

Nanocellulose Applications for Drug Delivery: A Review

  • Lee, Seung-Hwan;Kim, Hyun-Ji;Kim, Jin-Chul
    • Journal of Forest and Environmental Science
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    • v.35 no.3
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    • pp.141-149
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    • 2019
  • Nanocellulose, which can exist as either cellulose nanocrystals or cellulose nanofibrils, has been used as a biomaterial for drug delivery owing to its non-immunogenicity, biocompatibility, high specific area, good mechanical properties, and variability for chemical modification. Various water-soluble drugs can be bound to and released from nanocelluloses through electrostatic interactions. The high specific surface area of nanocellulose allows for high specific drug loading. Additionally, a broad spectrum of drugs can bind to nanocellulose after facile chemical modifications of its surface. Controlled release can be achieved for various pharmaceuticals when the nanocellulose surface is chemically modified or physically formulated in an adequate manner. This review summarizes the potential applications of nanocelluloses in drug delivery according to published studies on drug delivery systems.

Stimuli-Sensitive Poly(NIPA-co-APA) Hydrogels for the Controlled Release of Keterolac Tromethamine

  • Kim, Yonghyun;Babu, V. Ramesh;Rao, K.S.V. Krishna;Lim, Jae-Min;Thangadurai, T. Daniel;Lee, Yong-Ill
    • Journal of the Korean Chemical Society
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    • v.58 no.1
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    • pp.92-99
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    • 2014
  • The pH sensitive hydrogels composed of N-isopropylacrylamide (NIPA) and acryloyl phenylalanine (APA) were prepared by redox polymerization using N,N'-methylenebisacrylamide (MBA) as a crosslinker. Anti-inflammatory and analgesic agent, Keterolac Tromethamine (KT), was loaded successfully into poly(NIPA-co-APA) copolymeric hydrogels by swelling equilibrium method. To understand the nature of drug in the polymeric matrix, the newly synthesized drug loaded poly(NIPA-co-APA) copolymeric hydrogels were characterized by using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. The scanning electron microscopy (SEM) technique result indicates the spherical smooth surface of the hydrogels. The drug (KT) releasing nature of the poly(NIPA-co-APA) hydrogels was studied in pH 1.2 and 7.4. Effects of drug loading, crosslinking agent, pH and the ionic strength of the external medium on swelling of hydrogels were also investigated.

Improvement of a Context-aware Recommender System through User's Emotional State Prediction (사용자 감정 예측을 통한 상황인지 추천시스템의 개선)

  • Ahn, Hyunchul
    • Journal of Information Technology Applications and Management
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    • v.21 no.4
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    • pp.203-223
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    • 2014
  • This study proposes a novel context-aware recommender system, which is designed to recommend the items according to the customer's responses to the previously recommended item. In specific, our proposed system predicts the user's emotional state from his or her responses (such as facial expressions and movements) to the previous recommended item, and then it recommends the items that are similar to the previous one when his or her emotional state is estimated as positive. If the customer's emotional state on the previously recommended item is regarded as negative, the system recommends the items that have characteristics opposite to the previous item. Our proposed system consists of two sub modules-(1) emotion prediction module, and (2) responsive recommendation module. Emotion prediction module contains the emotion prediction model that predicts a customer's arousal level-a physiological and psychological state of being awake or reactive to stimuli-using the customer's reaction data including facial expressions and body movements, which can be measured using Microsoft's Kinect Sensor. Responsive recommendation module generates a recommendation list by using the results from the first module-emotion prediction module. If a customer shows a high level of arousal on the previously recommended item, the module recommends the items that are most similar to the previous item. Otherwise, it recommends the items that are most dissimilar to the previous one. In order to validate the performance and usefulness of the proposed recommender system, we conducted empirical validation. In total, 30 undergraduate students participated in the experiment. We used 100 trailers of Korean movies that had been released from 2009 to 2012 as the items for recommendation. For the experiment, we manually constructed Korean movie trailer DB which contains the fields such as release date, genre, director, writer, and actors. In order to check if the recommendation using customers' responses outperforms the recommendation using their demographic information, we compared them. The performance of the recommendation was measured using two metrics-satisfaction and arousal levels. Experimental results showed that the recommendation using customers' responses (i.e. our proposed system) outperformed the recommendation using their demographic information with statistical significance.

Anti-thrombotic activity of fermented rice bran extract with several oriental plants in vitro and in vivo (쌀겨발효추출물의 항혈전효과)

  • Jeon, Bo-Ra;Ji, Hyun Dong;Kim, Su Jung;Lee, Chun-Hee;Kim, Tae-Wan;Rhee, Man-Hee
    • Korean Journal of Veterinary Research
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    • v.55 no.4
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    • pp.233-240
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    • 2015
  • Although the effects of the rice bran have recently been investigated, there is no information regarding platelet physiology available. However, it is well known that fermented natural plants have a beneficial effect on cardiovascular diseases. Therefore, this study was conducted to investigate whether fermented rice bran extract (FRBE) with several plants (Artemisia princeps, Angelica Gigantis Radix, Cnidium officinale, and Camellia sinensis) affected agonist-induced platelet aggregation, and if so, what the underlying mechanism of its activity was. We performed several experiments, including in vitro platelet aggregation, intracellular calcium concentration and adenosine triphosphate release. In addition, the activation of integrin ${\alpha}_{II}b{\beta}3$ was determined using fibrinogen binding. Thrombus formation was also evaluated in vivo using an arterio-venous shunt model. The FRBE inhibited collagen-induced platelet aggregation in a concentration-dependent manner. FRBE significantly and dose dependently attenuated thrombus formation using rat arterio-venous shunt. FRBE suppressed the intracellular calcium mobilization in collagen-stimulated platelets. We also found that FRBE inhibited extracellular stimuli-responsive kinase 1/2, p38-mitogen-activated protein kinases and c-Jun N-terminal kinase phosphorylation. These results suggested that FRBE inhibited collagen-induced platelet aggregation, which was mediated by modulation of downstream signaling molecules. In conclusion, FRBE could be developed as a functional food against aberrant platelet activation-related cardiovascular diseases.

Adhesion-induced generation of oxygen free radical from human alveolar macrophages and its mechanisms (폐포대식세포의 부착에 의한 산소유리기 분비능 활성화 및 그 기전)

  • Chung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.210-220
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    • 1996
  • Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

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Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation

  • Jeong, Dahye;Irfan, Muhammad;Kim, Sung-Dae;Kim, Suk;Oh, Jun-Hwan;Park, Chae-Kyu;Kim, Hyun-Kyoung;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.548-555
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    • 2017
  • Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.